Dataset Information

LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling.

ABSTRACT: RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the Caenorhabditis elegans homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the C. elegans intestine. We show that LET-413 is a RAB-5 effector and colocalizes with RAB-10 on endosomes, and the overlap of LET-413 with RAB-10 is RAB-5 dependent. Notably, LET-413 enhances the interaction of DENN-4 with RAB-10(GDP) and promotes DENN-4 guanine nucleotide exchange factor activity toward RAB-10. Loss of LET-413 leads to cytosolic dispersion of the RAB-10 effectors TBC-2 and CNT-1. Finally, we demonstrate that the loss of RAB-10 or LET-413 results in abnormal overextensions of lateral membrane. Hence, our studies indicate that LET-413 is required for DENN-4-mediated RAB-10 activation, and the LET-413-assisted RAB-5 to RAB-10 cascade contributes to the integrity of C. elegans intestinal epithelia.

SUBMITTER: Liu H

PROVIDER: S-EPMC5748983 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling.

Liu Hang H Liu Hang H Wang Shimin S Hang Weijian W Gao Jinghu J Zhang Wenjuan W Cheng Zihang Z Yang Chao C He Jun J Zhou Jie J Chen Juan J Shi Anbing A

The Journal of cell biology 20171027 1

RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the <i>Caenorhabditis elegans</i> homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the <i>C. elegans</i> intestine. We show that LET-413 is a RAB-5 effector and colocalizes with ...[more]

PMID: 29079669

Similar Datasets

Project description:The facultative intracellular bacterium Legionella pneumophila proliferates within amoebae and human alveolar macrophages, and it is the causative agent of Legionnaires' disease, a life-threatening pneumonia. Within host cells, L. pneumophila establishes a replicative haven by delivering numerous effector proteins into the host cytosol, many of which target membrane trafficking by manipulating the function of Rab GTPases. The Legionella effector AnkX is a phosphocholine transferase that covalently modifies host Rab1 and Rab35. However, a detailed understanding of the biological consequence of Rab GTPase phosphocholination remains elusive. Here, we broaden the understanding of AnkX function by presenting three lines of evidence that it interferes with host endocytic recycling. First, using immunogold transmission electron microscopy, we determined that GFP-tagged AnkX ectopically produced in mammalian cells localizes at the plasma membrane and tubular membrane compartments, sites consistent with targeting the endocytic recycling pathway. Furthermore, the C-terminal region of AnkX was responsible for association with the plasma membrane, and we determined that this region was also able to bind the phosphoinositide lipids PI(3)P and PI(4)P in vitro. Second, we observed that mCherry-AnkX co-localized with Rab35, a regulator of recycling endocytosis and with major histocompatibility class I protein (MHC-I), a key immunoregulatory protein whose recycling from and back to the plasma membrane is Rab35-dependent. Third, we report that during infection of macrophages, AnkX is responsible for the disruption of endocytic recycling of transferrin, and AnkX's phosphocholination activity is critical for this function. These results support the hypothesis that AnkX targets endocytic recycling during host cell infection. Finally, we have demonstrated that the phosphocholination activity of AnkX is also critical for inhibiting fusion of the Legionella-containing vacuole (LCV) with lysosomes.

Dataset Information

LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling.

Publications

LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets