Dynein Is Required for Polarized Dendritic Transport and Uniform Microtubule Orientation in Axons

doi:10.1038/ncb1777

Journal List > NIHPA Author Manuscripts

Nat Cell Biol. Author manuscript; available in PMC 2009 April 1.

Published in final edited form as:

Nat Cell Biol. 2008 October; 10(10): 1172–1180.

Published online 2008 August 31. doi: 10.1038/ncb1777.

PMCID: PMC2588425

NIHMSID: NIHMS72200

Dynein Is Required for Polarized Dendritic Transport and Uniform Microtubule Orientation in Axons

Yi Zheng,^1,² Jill Wildonger,^1,² Bing Ye,¹ Ye Zhang,¹ Angela Kita,¹ Susan H. Younger,¹ Sabina Zimmerman,¹ Lily Yeh Jan,¹ and Yuh Nung Jan¹

¹ Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA

Correspondence should be addressed to Yuh Nung Jan (Email: yuhnung.jan/at/ucsf.edu)

²these authors contributed equally to this work.

Author contributions: Y. Zheng, J.W., S.H.Y. and Y.N.J. conceived and designed the project. Y. Zheng, J.W., A.K. and S.H.Y. carried out the genetic screen. B.Y. and Y. Zhang completed the Golgi outpost analysis and S.Z. analyzed the EB1-GFP movies. Y. Zheng and J.W. performed all other experiments and contributed equally to this fwork. Y. Zheng, J.W. L.Y.J. and Y.N.J. wrote the paper. All authors read and edited the manuscript.

The publisher's final edited version of this article is available at Nat Cell Biol.

See commentary "Dynein branches out." in Nat Cell Biol, volume 10 on page 1131.

See other articles in PMC that cite the published article.

Abstract

Axons and dendrites differ in both microtubule (MT) organization and in the organelles and proteins they contain. Here we show that the MT motor dynein plays a critical role in polarized transport and in controlling the orientation of axonal MTs in fly dendritic arborisation (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal MTs are normally oriented uniformly plus end-distal, but without dynein axons contain both plus and minus end-distal MTs. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal MTs are no longer uniform in polarity.

The differential distribution of organelles and proteins to distinct compartments within cells is critical to their specialized functions. Proteins and organelles are transported to different subcellular compartments by the MT motors dynein and kinesin. The multi-subunit dynein complex travels towards MT minus ends whereas the majority of kinesins travel towards MT plus ends. Cargo localization depends on motor activity and MT organization¹. In neurons, the signal-sending axons contain MTs that are oriented uniformly plus end-distal, whereas the signal-receiving dendrites have MTs whose orientation is mixed². How might this difference in MT orientation be created? Dynein and kinesin not only move along MTs, but can also transport MTs³. Without the kinesin CHO1/MKLP the orientation of dendritic MTs are uniformly plus end-distal, rather than mixed, raising the possibility that MT motors may regulate MT polarity⁴^,⁵. Whether dynein contributes to MT orientation in neurons remains an outstanding question.

Similar to most mammalian neurons, the fly dendritic arborisation (da) neurons have distinct axonal and dendritic compartments⁶^–⁹, and their MT organization resembles that in typical mammalian neurons⁶^,⁷. In a genetic screen we uncovered mutations in components of the dynein complex, dynein light intermediate chain 2 (dlic2) and dynein intermediate chain (dic, also called short wing), that cause a proximal shift in both organelle distribution and branch position within mutant dendritic arbours. These dynein mutations cause dendritic cargo to be mislocalized to axons and result in mixed orientation of axonal MTs. Our results provide new insight into the function of dynein in neurons, including hitherto unrecognized roles in polarized dendritic targeting and in regulating MT polarity.

A forward genetic screen uncovered mutations in the dynein complex components Dlic2 and Dic causing radical changes in da neuron dendritic arbour patterning (see Supplementary Information, Fig. S1). Mosaic analysis revealed that removing Dlic2 specifically within da neurons resulted in a drastic reduction in dendrite arborisation with greatly reduced receptive field coverage (control: 16,903 ± 3,292 μm; dlic2¹¹⁵⁷: 3,671 ± 681 μm, p<0.001; data represent mean ± standard deviation; n=4; Fig. 1a,b,f

; Supplementary Information, Fig. S4, and data not shown). Not only was there a reduction in the total number of branch points (control: 499 ± 124, n=4; dlic2¹¹⁵⁷: 140 ± 29, p<0.01; n=4; Fig. 1g

), fewer branches were located distally (Fig. 1b

′) while the proximal dendrites branched profusely (Fig. 1b

″), revealing a dramatic proximal shift in branch distribution (Fig. 1e

). Also, most dlic2¹¹⁵⁷ axons are abnormally thick and many appear to have split, or branched, into multiple neurites a short distance from the soma (Fig. 1h

; Supplementary Information, Fig. S2). The multiple neurites of the mutant da neurons bundle with other axons in the nerve, although only one neurite fully extends into the ventral nerve cord (VNC) (Supplementary Information, Fig. S2). These dendritic and axon phenotypes are rescued by neuronal expression of UAS-dlic2-eGFP (Fig. 1d

). Likewise, a dic+ transgene rescues the lethality and phenotypes of dic¹²²⁹ animals (Supplementary Information, Fig. S3). In addition, dynein heavy chain (dhc) clones exhibited a similar, although less severe, phenotype (possibly due to differential perdurance of Dhc versus Dlic2; Supplementary Information, Fig. S3), and loss of Lis1, which interacts with dynein, phenocopies dlic2¹¹⁵⁷ (Fig. 1c

, and Supplementary Information, Fig. S3). We therefore conclude that these phenotypes result from a loss of dynein function.

Figure 1

dlic2¹¹⁵⁷ Functions Cell-Autonomously to Regulate Dendrite and Axon Development

Dynein mediates the subcellular localization of Golgi¹⁰. In mammalian and fly neurons, Golgi structures in the form of “outposts” localize to dendrites and influence branching⁸^,¹¹. Indeed, distal dlic2¹¹⁵⁷ dendritic arbours displayed a nearly four-fold decrease in the number and size of Golgi outposts, which were marked by Mannosidase II-eGFP (ManII-eGFP) (number per 100 μm: control: 7.92 ± 3.11, n=6; dlic2¹¹⁵⁷: 2.00 ± 2.00, p<0.025, n=3; total size per 100 μm: control: 1.12 ± 0.36 μm², n=6; dlic2¹¹⁵⁷: 0.25 ± 0.25 μm², n=3, p<0.01; Fig. 2g,h,k,l

). In contrast, there was a significant increase in the number and size of Golgi outposts in the proximal dlic2¹¹⁵⁷ dendritic arbours (number within 30 μm from soma: control: 10.00 ± 3.39, n=5; dlic2¹¹⁵⁷: 15.45 ± 4.18, n=11, p<0.025; total size within 30 μm from soma: control: 3.31 ± 1.08 μm², n=5; dlic2¹¹⁵⁷: 6.00 ± 1.75 μm², n=11, p<0.01; Fig. 2a,b,e,f,k,l

). This change in Golgi outpost distribution (reduced distally, increased proximally) thus parallels the change in branch distribution.

Figure 2

Loss of Dynein Function Alters Golgi Outpost Distribution

In contrast to the scarcity of Golgi outposts in wild type axons⁸ (Fig. 2a,c,k

), there was a striking increase in Golgi outpost number in dlic2¹¹⁵⁷ axons (number per 100 μm: control: 2.33 ± 2.71, n=6; dlic2¹¹⁵⁷: 34.49 ± 14.55, n=5, p<0.001; Fig. 2a–d,k

). Golgi outpost distribution was similarly altered in the axons of dic¹²²⁹/dic^ts larvae (control: 1.43 ± 1.69 per 100 μm, n=19; dic¹²²⁹/dic^ts: 15.36 ± 7.29, n=11, p<0.001), which survive to 3^rd instar and whose da neurons exhibit similar, though milder, dendrite and axon defects (Supplementary Information, Fig. S3). Live imaging of ManII-eGFP in dic¹²²⁹/dic^ts neurons further revealed Golgi outposts moving from the soma into the axon and travelling anterogradely and retrogradely within the axon (Fig. 2i,j

, Supplementary Information, Movies 3 and 4 and Supplementary Table 1). In contrast, in control axons, the Golgi outposts that were occasionally present were stationary, and we did not observe any Golgi outposts moving from the soma into the axon (Fig. 2i

). These results suggest dynein actively prevents Golgi outposts from entering axons in wild type neurons.

Dynein also transports endosomes¹², which regulate dendritic membrane supply¹³^,¹⁴. Indeed, disrupting endosomal function alters dendrite morphogenesis, including branch formation¹⁵. Normally, the recycling and early endsomal marker Rab4-RFP and the late endosome and lysosome marker Spinster (Spin)-RFP localize to both axons and dendrites (Fig. 3a,a′,c,c′

). In dic¹²²⁹/dic^ts and dlic2¹¹⁵⁷ neurons, Rab4-RFP and Spin-RFP are virtually absent from dendrites (Fig. 3b,b′,d,d′

and Supplementary Information, Fig. S5) but are still present in axons, suggesting that dynein is required for the dendritic localization of endosomes.

Figure 3

Localization of Endosomes and the Ion Channel Ppk Depends on Dynein

We hypothesized that as Dlic2 decreases over time in dlic2¹¹⁵⁷ clones, Golgi outposts and endosomes would fail to travel distally, and new branches would only be added proximally. Indeed, time lapse analysis revealed proximal branch dynamics increased in dlic2¹¹⁵⁷ dendritic arbours and the change in branch dynamics correlated with Golgi outpost position (Supplementary Information, Fig S6), suggesting that machinery (including Golgi outposts) required for branch growth and dynamics accumulate proximally in dynein mutant neurons.

Next we examined the localization of Pickpocket (Ppk), which belongs to a family of conserved degenerin/epithelial sodium channels that likely function as sensory channels¹⁶. Whereas Ppk is normally detectable at low levels in dendrites but not in axons¹⁷ (Fig. 3e,e′

), in dlic2¹¹⁵⁷ clones Ppk was present in both dendrites and axons (Fig. 3f,f′

Besides transporting organelles and proteins, dynein also transports MTs within axons, leading us to investigate if axonal MT organization is impacted by the loss of dynein function. First we used the MT minus end marker Nod-βgal, a chimera comprised of the Nod motor domain fused to the Kinesin1 (Kin1) coiled-coiled domain and β-galactosidase¹⁸. Although full length Nod preferentially binds MT plus ends¹⁹, the Nod-βgal chimera localizes to MT minus ends in multiple cell types and is commonly used as a MT minus end marker¹⁸ (Supplementary Information, Fig. S7). In fly neurons, including da neurons, Nod-βgal localizes specifically to dendrites⁶^–⁹^,¹⁸^,²⁰^,²¹ (Fig. 4a,a′

). In dlic2¹¹⁵⁷ clones and in dic¹²²⁹/dic^ts neurons Nod-βgal was still present in dendrites but frequently localized to axons as well (36% of dlic2¹¹⁵⁷ ddaC axons (n=11) and 30% of dic¹²²⁹/dic^ts ddaC axons (n=15) showed strong Nod-βgal signal; Fig. 4b,b′,c,c′

). The amount of Nod-βgal in the mutant axons was variable and did not correlate with the formation of ectopic neurites or axonal width. These results are consistent with the finding that Nod-βgal localizes to the axons of fly photoreceptor neurons expressing a dominant-negative form of Glued²², which is a component of the dynactin complex that is necessary for dynein function²³. Over-expressing another dynactin complex member, dynamitin (dmn), also interferes with dynein function²³. ddaC neurons over-expressing dmn exhibited dendritic and axonal morphology defects similar to dlic2¹¹⁵⁷ and dic¹²²⁹/dic^ts, and Nod-βgal was ectopically localized to axons (50% of ppk-Gal4 UAS-dmn axons had strong Nod-βgal signal, n=30; Fig. 4d,d′

Figure 4

Mislocalization of Nod-βgal, but not Kin-βgal, in Dynein Mutant Neurons

Next we employed the axon specific marker Kin-βgal¹⁸^,²⁴, which is comprised of the Kin1 motor and coiled-coiled domains together with β-galactosidase, and found it is localized exclusively to axons in all three different dynein loss-of-function scenarios as in control neurons (Fig. 4e–h

). Additionally, pre-synaptic components such as Cystein string protein (Csp), Bruchpilot and Syntaxin localized normally in dic¹²²⁹/dic^ts neurons (data not shown), although there are axonal “cargo jams” indicative of defects in axonal transport (Supplementary Fig. S7).

The ectopic axonal localization of Nod-βgal in dynein loss-of-function neurons suggests a change in MT polarity. To further analyze MT orientation we utilized EB1-GFP, which binds growing MT plus ends and takes on a comet-like appearance as the MT grows. In fly PNS axons EB1-GFP always moves away from the soma (anterograde)⁷, indicating the axonal MTs are orientated with their plus ends-distal, as in mammalian neurons². Similar to control neurons (Fig. 5a,b,e

; Table 1 and Supplementary Information, Movie 1), in dic¹²²⁹/dic^ts axons EB1-GFP always moved anterogradely during 2^nd instar (Table 1); however, during 3^rd instar, a third of the EB1-GFP comets travelled retrogradely (Fig. 5c–e

; Table 1 and Supplementary Information, Movie 2). Similar abnormal EB1-GFP movements occurred in dlic2¹¹⁵⁷ clones (Supplementary Information, Movie 5) and in neurons over-expressing dmn (40% retrograde, 60% anterograde, n=177; Supplementary Information, Movie 6). The loss of dynein function also affects EB1-GFP movement in the axons of class I da neurons (control: 100% anterograde, n=96; dic¹²²⁹/dic^ts 19% retrograde, 81% anterograde, n=80; Fig. 5e

), even though dic¹²²⁹/dic^ts class I axons are not noticeably enlarged, nor do they have ectopic branches. Whereas the loss of dynein function perturbed the orientation of axonal MTs, the orientation of dendritic MTs appeared normal. The direction and rate of EB1-GFP movement in dendrites was comparable between control (rate: 6.49 ± 2.16 μm/min; 96% retrograde, 4% anterograde; n=75) and dic¹²²⁹/dic^ts (rate: 6.37 ± 1.95 μm/min; 98% retrograde, 2% anterograde; n=64). Thus, the loss of dynein activity disrupts the uniform orientation of MTs in axons without causing a detectable effect on the orientation of dendritic MTs.

Figure 5

Mixed Orientation of Axonal MTs in dic¹²²⁹/dic^ts Neurons Revealed by EB1-GFP

Table 1

Direction and Rate of EB1-GFP Comets in the Axons of Control and dic¹²²⁹/dic^ts ddaC Neurons

Proper cellular morphology and function depends on the polarized localization of organelles and proteins to specific subcellular compartments. In this study, we show that dynein plays a crucial role in dendrite arbour patterning and in organizing distinct functional compartments (the axon and dendrites) of a neuron. The position of branches within a dendritic arbour has a key role in determining the inputs a neuron receives from pre-synaptic axons or, in the case of sensory neurons, the local environment. We show here that dynein is necessary for proper positioning of dendritic branches relative to the soma. As a motor, dynein likely influences branch formation by mediating the distribution of cargos that affect branch growth and dynamics. Notwithstanding an overall decrease in dendrite extension and branching in dynein mutants, time-lapse analysis of a few dendrites revealed that they extend normally but have fewer and less stable terminal branches, suggesting that decreased terminal branching is not simply caused by a decrease in dendrite growth. One likely explanation is that “branching machinery” (including Golgi outposts, endosomes and potentially other proteins and/or organelles) that are normally transported distally for dendrite extension and maintenance become trapped in the proximal arbour in the dynein mutant neurons, resulting in decreased distal branching and the formation of ectopic branches close to the cell body.

Without dynein, Golgi outposts and Ppk are present ectopically in axons, revealing a previously unappreciated role for dynein in mediating the dendrite-specific localization of organelles and proteins. One possible explanation for axonal mislocalization is that Golgi outposts and Ppk interact with a MT plus end-directed motor (e.g., kinesin) that transports them into axons in the absence of dynein. Dynein might normally transports such cargo directly to dendrites; alternatively, it is also possible that cargo first enters axons but that dynein counter-acts kinesin and carries this cargo out of axons. Since we never observed Golgi outposts moving from the soma into the axon in wild type neurons, our data favour the former possibility. In contrast to the mislocalization of dendritic protein and organelles, Kin-βgal and proteins destined for the axonal terminal retain their polarized distribution, perhaps to be expected given that kinesin mediates the majority of anterograde axonal transport¹.

In mammalian and fly neurons, axonal MTs are arrayed plus end-distal whereas dendritic MT orientation is mixed²^,⁷. A long-standing question concerns the mechanism(s) that establish and maintain different MT orientations in axons and dendrites. Loss of dynein function causes the axonal localization of Nod-βgal and retrograde movement of EB1-GFP, indicating that minus end-distal MTs are present in these mutant axons. How might dynein regulate the orientation of axonal MTs? The sliding filament model of axonal MT transport proposes that a subset of dynein in the axon is stationary (via an interaction with stable MTs and/or actin) and that dynein’s motor domain interacts with short MT polymers, propelling plus end-distal MTs down the axon as the motor moves to the MT minus end³. Our in vivo data support the idea that in addition to transporting MTs, dynein functions as a “gatekeeper” to move minus end-distal MTs towards the soma, excluding them from the axon. Neurons lacking functional dynein would still transport MTs, likely via kinesin³, but now minus end-distal MTs would infiltrate the axon. Proximal axons likely have unique properties¹, providing a possible explanation for how minus end distal MTs would be excluded from axons but not dendrites.

Recent studies indicate that the trans Golgi network (TGN), which comprises part of the Golgi outposts²⁵^,²⁶, can also function as a MT organizing center (MTOC)²⁷^,²⁸ and influence MT organization. Although it is conceivable that Golgi outposts mislocalized to dynein mutant axons could alter MT polarity, expressing lava lamp^{dominant-negative}, which prevents Golgi from associating with dynein without affecting dynein function²⁹, causes Golgi outposts to mislocalize to axons without altering MT orientation (Ye et al., 2007 and unpublished observations). Moreover, the change in axonal MT orientation is not likely to be simply a consequence of altered axon morphology because the loss of dynein function also alters the MT orientation of class I neuron axons, which appear relatively normal. With our current level of understanding, the model in which dynein acts as a “gatekeeper” is most consistent with our results and the findings of others.

METHODS

Mutagenesis and Mapping

EMS mutagenesis was performed according to standard protocols. Briefly, male flies were fed 20 mM EMS to induce mutations on an isogenic FRT 19A chromosome. We screened the live embryonic and larval progeny of approximately 1,900 lethal lines and recovered 112 mutants that affect dendrite and/or axon morphogenesis. Mutations were mapped using X chromosome duplications and deficiencies from Bloomington, followed by complementation tests with known mutants (see Supplemental Information for additional details).

Fly Stocks

dlic2¹¹⁵⁷ and dic¹²²⁹ were generated by EMS mutagenesis as described above. Both mutations cause lethality during the 2^nd larval instar. The following lines were generously shared: FRT G13 lis1^G10.14 and FRT 2A dhc64C⁴^–¹⁹ (L. Luo), UAS-EB1-GFP (T. Uemura), UAS-dmn (R. Warrior), dic+ transgene (T. Hays), and UAS-Spin-RFP (S. Sweeney). UAS-Rab4-RFP, dic^ts and lis1⁴^–¹⁹ are from Bloomington. To generate UAS-dlic2-eGFP flies, dlic2 cDNA from the Drosophila Genomics Resource Center was cloned into a modified pUAST vector so that eGFP was fused in frame to the Dlic2 C-terminus; transgenic flies were generated according to standard protocols. UAS-dmn was over-expressed in class IV neurons using ppk-Gal4 and 4-77-Gal4.

Clonal Analysis

Clonal analysis (MARCM) was performed as previously described⁸^,³⁰. Briefly, embryos were collected on grape plates for 2 hr, allowed to develop for 2 hr at 25°C and heat shocked for 45 min twice at 38°C with a 30 min rest in between. Larvae with da neuron clones were selected and examined by either live imaging or immunohistochemistry. For da neuron clone analysis yw hs-flp tub-Gal80 FRT 19A; 109(2)80-Gal4 UAS-mCD8-GFP flies were mated with: (1) yw FRT 19A (control), (2) yw dlic2¹¹⁵⁷ FRT 19A and (3) yw dlic2¹¹⁵⁷ FRT 19A; UAS-dlic2-eGFP (dlic2+ rescue). The location of dic between the centromere and FRT 19A has prevented us from generating loss-of-function clones, so we focused on the phenotypes displayed in dlic2¹¹⁵⁷ clones. lis1 clones: yw hs-flp elav-Gal4 UAS-mCD8-GFP; FRT G13 lis1^G10.14/FRT G13 hs-flp tub-Gal80. dhc64C clones: yw hs-flp elav-Gal4 UAS-mCD8-GFP; FRT 2A dhc64C⁴–¹⁹/FRT 2A tub-Gal80. For Golgi outpost analysis yw hs-flp tub-Gal80 FRT 19A; 109(2)80-Gal4 UAS-ManII-eGFP flies were mated with: (1) yw FRT 19A; UAS-mCD8-dsRed (control) and (2) yw dlic2¹¹⁵⁷ FRT 19A; UAS-mCD8-dsRed. The number and size of Golgi outposts in fixed (Fig. 3a–h,k,l

) and live samples (Fig. 3i,j

) were quantified using ImageJ. We sampled two domains of the wild type and mutant dendritic arbours: a proximal domain, which included all dendrites within a 30 μm radius from the soma, and a distal domain, which encompassed an 100 μm segment of the distal part of major dendrites that extended towards the dorsal midline.

Live Imaging and Analysis of EB1-GFP

2^nd or 3^rd instar larvae of the following genotypes were imaged: (1) 4-77-Gal4 UAS-mRFP; UAS-EB1-GFP (control), (2) dic¹²²⁹/dic^ts; 4-77-Gal4 UAS-mRFP; UAS-EB1-GFP, (3) 2-21-Gal4/UAS-EB1-GFP (control) and (4) dic¹²²⁹/dic^ts; 2-21-Gal4/UAS-EB1-GFP. Larvae were washed briefly in 1X PBS before mounting in halocarbon oil for live imaging of ddaC (class IV) and ddaE (class I) neurons. Larvae were imaged on average 5–15 min but no longer than 25 min on a Zeiss LSM 510 confocal microscope. Movies of EB1-GFP comets were made by imaging axons or dendrites every second for 1.5 to 6.5 min. For each genotype multiple larvae were imaged. EB1-GFP direction and rate were calculated using ImageJ (NIH), which was also used to generate the kymographs.

Immunohistochemistry and Dendrite Analysis

3^rd instar larvae were fixed according to standard protocols³⁰. The following antibodies were used: rabbit anti-βgal, 1/5000 (Cappel); rat anti-mCD8, 1/100 (Invitrogen); rabbit anti-GFP, 1/3000; rabbit, anti-Ppk 1/800 (generously provided by W. Johnson); mouse 22C10, 1/100 (DSHB); Cy3-conjugated anti-HRP, 1/1000 (Jackson ImmunoResearch). In the Figures, we label the neurites that extend within the intersegmental nerve (ISN) as axons; however, as described in the text, these neurites contain proteins and organelles that are normally found specifically in dendrites. Dendrite analysis was performed using Neurolucida.

Statistical analysis

All statistical tests were performed with two-tailed Student t-test according to standard methods.

Supplementary Material

SupData

Click here to view.^{(2.3M, pdf)}

Acknowledgments

We would like to thank T. Uemura, F.B. Gao, L. Luo, R. Warrior, T. Hays and the Bloomington Stock Center for fly stocks; W. Song, C. Han, S. Zhu, P. Soba, J. Parrish, J. Kardon and S. Reck-Peterson for helpful suggestions and comments on the manuscript and members of the Jan Lab for stimulating discussions. We thank T. Uemura for communicating results prior to publication. This work was supported by Kirschstein NRSA fellowships F32-MH75223 (Y. Zheng), F32-HD53199 (J.W.), a NIH Pathway to Independence Award K99MH080599 (B.Y.), a graduate fellowship from Genentech, Inc. and the Sandler Family Supporting Foundation (Y. Zhang) and NIH grants R01NS40929 and RO1NS47200 (Y.N.J.). Y.N.J. and L.Y.J. are Investigators of the Howard Hughes Medical Institute.

References

1. Hirokawa N, Takemura R. Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci. 2005;6:201–214. [PubMed]

2. Baas PW, Deitch JS, Black MM, Banker GA. Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc Natl Acad Sci U S A. 1988;85:8335–8339. [PubMed]

3. Baas PW, Vidya Nadar C, Myers KA. Axonal transport of microtubules: the long and short of it. Traffic. 2006;7:490–498. [PubMed]

4. Sharp DJ, et al. Identification of a microtubule-associated motor protein essential for dendritic differentiation. J Cell Biol. 1997;138:833–843. [PubMed]

5. Yu W, et al. Depletion of a microtubule-associated motor protein induces the loss of dendritic identity. J Neurosci. 2000;20:5782–5791. [PubMed]

6. Andersen R, Li Y, Resseguie M, Brenman JE. Calcium/calmodulin-dependent protein kinase II alters structural plasticity and cytoskeletal dynamics in Drosophila. J Neurosci. 2005;25:8878–8888. [PubMed]

7. Rolls MM, et al. Polarity and intracellular compartmentalization of Drosophila neurons. Neural Develop. 2007;2:7–20. [PubMed]

8. Ye B, et al. Growing Dendrites and Axons Differ in Their Reliance on the Secretory Pathway. Cell. 2007;130:717–729. [PubMed]

9. Yamamoto M, Ueda R, Takahashi K, Saigo K, Uemura T. Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuronglia interface. Curr Biol. 2006;16:1678–1683. [PubMed]

10. Allan VJ, Thompson HM, McNiven MA. Motoring around the Golgi. Nat Cell Biol. 2002;4:E236–242. [PubMed]

11. Horton AC, et al. Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis. Neuron. 2005;48:757–771. [PubMed]

12. Murray JW, Wolkoff AW. Roles of the cytoskeleton and motor proteins in endocytic sorting. Adv Drug Deliv Rev. 2003;55:1385–1403. [PubMed]

13. Park M, et al. Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron. 2006;52:817–830. [PubMed]

14. Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD. Recycling endosomes supply AMPA receptors for LTP. Science. 2004;305:1972–1975. [PubMed]

15. Sweeney NT, Brenman JE, Jan YN, Gao FB. The coiled-coil protein shrub controls neuronal morphogenesis in Drosophila. Curr Biol. 2006;16:1006–1011. [PubMed]

16. Ernstrom GG, Chalfie M. Genetics of sensory mechanotransduction. Annu Rev Genet. 2002;36:411–453. [PubMed]

17. Adams CM, et al. Ripped pocket and pickpocket, novel Drosophila DEG/ENaC subunits expressed in early development and in mechanosensory neurons. J Cell Biol. 1998;140:143–152. [PubMed]

18. Clark IE, Jan LY, Jan YN. Reciprocal localization of Nod and kinesin fusion proteins indicates microtubule polarity in the Drosophila oocyte, epithelium, neuron and muscle. Development. 1997;124:461–470. [PubMed]

19. Cui W, et al. Drosophila Nod protein binds preferentially to the plus ends of microtubules and promotes microtubule polymerization in vitro. Mol Biol Cell. 2005;16:5400–5409. [PubMed]

20. Sanchez-Soriano N, et al. Are dendrites in Drosophila homologous to vertebrate dendrites? Dev Biol. 2005;288:126–138. [PubMed]

21. Lee T, Winter C, Marticke SS, Lee A, Luo L. Essential roles of Drosophila RhoA in the regulation of neuroblast proliferation and dendritic but not axonal morphogenesis. Neuron. 2000;25:307–316. [PubMed]

22. Whited JL, Cassell A, Brouillette M, Garrity PA. Dynactin is required to maintain nuclear position within postmitotic Drosophila photoreceptor neurons. Development. 2004;131:4677–4686. [PubMed]

23. Welte MA. Bidirectional transport along microtubules. Curr Biol. 2004;14:R525–537. [PubMed]

24. Giniger E, Wells W, Jan LY, Jan YN. Tracing neurons with a kinesin-beta-galactosidase fusion protein. Roux’s Archives of Developmental Biology. 1993;202:112–122.

25. Pierce JP, Mayer T, McCarthy JB. Evidence for a satellite secretory pathway in neuronal dendritic spines. Curr Biol. 2001;11:351–355. [PubMed]

26. Sytnyk V, et al. Neural cell adhesion molecule promotes accumulation of TGN organelles at sites of neuron-to-neuron contacts. J Cell Biol. 2002;159:649–661. [PubMed]

27. Chabin-Brion K, et al. The Golgi complex is a microtubule-organizing organelle. Mol Biol Cell. 2001;12:2047–2060. [PubMed]

28. Efimov A, et al. Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network. Dev Cell. 2007;12:917–930. [PubMed]

29. Papoulas O, Hays TS, Sisson JC. The golgin Lava lamp mediates dynein-based Golgi movements during Drosophila cellularization. Nat Cell Biol. 2005;7:612–618. [PubMed]

30. Grueber WB, Jan LY, Jan YN. Tiling of the Drosophila epidermis by multidendritic sensory neurons. Development. 2002;129:2867–2878. [PubMed]

Formats:

PubMed articles by these authors

PubMed related articles

Recent Activity

Links

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information