Endocytic Crosstalk: Cavins, Caveolins, and Caveolae Regulate Clathrin-Independent Endocytosis

Chaudhary, Natasha, Gomez, Guillermo A., Howes, Mark T., Lo, Harriet P., McMahon, Kerrie-Ann, Rae, James A., Schieber, Nicole L., Hill, Michelle M., Gaus, Katharina, Yap, Alpha S. and Parton, Robert G. (2014) Endocytic Crosstalk: Cavins, Caveolins, and Caveolae Regulate Clathrin-Independent Endocytosis. PLoS Biology, 12 4: e1001832.1-e1001832.20. doi:10.1371/journal.pbio.1001832

Author Chaudhary, Natasha
Gomez, Guillermo A.
Howes, Mark T.
Lo, Harriet P.
McMahon, Kerrie-Ann
Rae, James A.
Schieber, Nicole L.
Hill, Michelle M.
Gaus, Katharina
Yap, Alpha S.
Parton, Robert G.
Title Endocytic Crosstalk: Cavins, Caveolins, and Caveolae Regulate Clathrin-Independent Endocytosis
Journal name PLoS Biology   Check publisher's open access policy
ISSN 1544-9173
Publication date 2014-04-08
Sub-type Article (original research)
DOI 10.1371/journal.pbio.1001832
Open Access Status DOI
Volume 12
Issue 4
Start page e1001832.1
End page e1001832.20
Total pages 20
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2015
Language eng
Abstract Several studies have suggested crosstalk between different clathrin-independent endocytic pathways. However, the molecular mechanisms and functional relevance of these interactions are unclear. Caveolins and cavins are crucial components of caveolae, specialized microdomains that also constitute an endocytic route. Here we show that specific caveolar proteins are independently acting negative regulators of clathrin-independent endocytosis. Cavin-1 and Cavin-3, but not Cavin-2 or Cavin-4, are potent inhibitors of the clathrin-independent carriers/GPI-AP enriched early endosomal compartment (CLIC/GEEC) endocytic pathway, in a process independent of caveola formation. Caveolin-1 (CAV1) and CAV3 also inhibit the CLIC/GEEC pathway upon over-expression. Expression of caveolar protein leads to reduction in formation of early CLIC/GEEC carriers, as detected by quantitative electron microscopy analysis. Furthermore, the CLIC/GEEC pathway is upregulated in cells lacking CAV1/Cavin-1 or with reduced expression of Cavin-1 and Cavin-3. Inhibition by caveolins can be mimicked by the isolated caveolin scaffolding domain and is associated with perturbed diffusion of lipid microdomain components, as revealed by fluorescence recovery after photobleaching (FRAP) studies. In the absence of cavins (and caveolae) CAV1 is itself endocytosed preferentially through the CLIC/GEEC pathway, but the pathway loses polarization and sorting attributes with consequences for membrane dynamics and endocytic polarization in migrating cells and adult muscle tissue. We also found that noncaveolar Cavin-1 can act as a modulator for the activity of the key regulator of the CLIC/GEEC pathway, Cdc42. This work provides new insights into the regulation of noncaveolar clathrin-independent endocytosis by specific caveolar proteins, illustrating multiple levels of crosstalk between these pathways. We show for the first time a role for specific cavins in regulating the CLIC/GEEC pathway, provide a new tool to study this pathway, identify caveola-independent functions of the cavins and propose a novel mechanism for inhibition of the CLIC/GEEC pathway by caveolin.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 19 times in Scopus Article | Citations
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Created: Wed, 21 May 2014, 12:22:03 EST by Susan Allen on behalf of Institute for Molecular Bioscience