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J Cell Sci. 2019 Feb 11;132(3). pii: jcs220749. doi: 10.1242/jcs.220749.

A global analysis of IFT-A function reveals specialization for transport of membrane-associated proteins into cilia.

Author information

1
Division of Cell Biology and Imaging, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
2
Department of Biology, Salem State University, Salem, MA 01970, USA.
3
Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
4
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
5
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
6
Division of Cell Biology and Imaging, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA George.Witman@umassmed.edu.

Abstract

Intraflagellar transport (IFT), which is essential for the formation and function of cilia in most organisms, is the trafficking of IFT trains (i.e. assemblies of IFT particles) that carry cargo within the cilium. Defects in IFT cause several human diseases. IFT trains contain the complexes IFT-A and IFT-B. To dissect the functions of these complexes, we studied a Chlamydomonas mutant that is null for the IFT-A protein IFT140. The mutation had no effect on IFT-B but destabilized IFT-A, preventing flagella assembly. Therefore, IFT-A assembly requires IFT140. Truncated IFT140, which lacks the N-terminal WD repeats of the protein, partially rescued IFT and supported formation of half-length flagella that contained normal levels of IFT-B but greatly reduced amounts of IFT-A. The axonemes of these flagella had normal ultrastructure and, as investigated by SDS-PAGE, normal composition. However, composition of the flagellar 'membrane+matrix' was abnormal. Analysis of the latter fraction by mass spectrometry revealed decreases in small GTPases, lipid-anchored proteins and cell signaling proteins. Thus, IFT-A is specialized for the import of membrane-associated proteins. Abnormal levels of the latter are likely to account for the multiple phenotypes of patients with defects in IFT140.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

BBSome; Flagella; GTPases; Intraflagellar transport; Jeune asphyxiating thoracic dystrophy (JATD); Mainzer-Saldino syndrome (MSS)

PMID:
30659111
PMCID:
PMC6382014
[Available on 2020-02-01]
DOI:
10.1242/jcs.220749

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