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The Rho-specific GAP protein DLC3 coordinates endocytic membrane trafficking

Braun, Anja C., Hendrick, Janina, Eisler, Stephan A., Schmid, Simone, Hausser, Angelika, Olayioye, Monilola A.·2015·Journal of Cell Science
DOI 10.1242/jcs.163857
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Abstract

Membrane trafficking is known to be coordinated by small GTPases, but the identity of their regulators, the guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that ensure balanced GTPase activation at different subcellular sites is largely elusive. Here, we show in living cells that deleted in liver cancer 3 (DLC3, also known as STARD8) is a functional Rho-specific GAP protein, the loss of which enhances perinuclear RhoA activity. DLC3 is recruited to Rab8-positive membrane tubules and is required for the integrity of the Rab8 and Golgi compartments. Depletion of DLC3 impairs the transport of internalized transferrin to the endocytic recycling compartment (ERC), which is restored by the simultaneous downregulation of RhoA and RhoB. We further demonstrate that DLC3 loss interferes with epidermal growth factor receptor (EGFR) degradation associated with prolonged receptor signaling. Taken together, these findings identify DLC3 as a novel component of the endocytic trafficking machinery, wherein it maintains organelle integrity and regulates membrane transport through the control of Rho activity.

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  • The accumulation of EGF in a RAB4-positive recycling compartment upon pathogenic LRRK2 expression or RNAi of either RAB8A or RAB10 reflects a crosstalk between recycling and degradative trafficking pathways.

    “The accumulation of EGF in a RAB4-positive recycling compartment upon pathogenic LRRK2 expression or RNAi of either RAB8A or RAB10 reflects a crosstalk between recycling and degradative trafficking pathways, which has been described before [64,65,66].”

    From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [65]

  • Interfering with the integrity/function of the RAB8-positive early recycling compartment causes impaired degradation of the EGFR, which consequently accumulates in a RAB4-positive recycling compartment.

    “and interfering with the integrity/function of the RAB8-positive early recycling compartment causes impaired degradation of the EGFR, which consequently accumulates in a RAB4-positive recycling compartment [65].”

    From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [65]

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Metadata

Authors
Braun, A. C., Hendrick, J., Eisler, S. A., Schmid, S., Hausser, A., & Olayioye, M. A.
Affiliations
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2015-04-01
Volume
128
Issue
7
Pages
1386-1399
ISSN
  • 1477-9137
  • 0021-9533
DOI
10.1242/jcs.163857
Cited by
41
References
0
Language
en

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