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J Cell Biol. 2017 Aug 7;216(8):2499-2513. doi: 10.1083/jcb.201704068. Epub 2017 Jun 19.

Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

Author information

1
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA.
2
National Center for Microscopy and Imaging Research and Center for Research on Biological Systems, University of California, San Diego, La Jolla, CA.
3
Department of Neurosciences, University of California, San Diego, La Jolla, CA.
4
Salk Institute for Biological Studies, San Diego, CA.
5
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA gpatrick@ucsd.edu.

Abstract

In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins.

PMID:
28630145
PMCID:
PMC5551717
DOI:
10.1083/jcb.201704068
[Indexed for MEDLINE]
Free PMC Article

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