The novel Rac effector RIN-1 regulates neuronal cell migration and axon pathfinding in C. <i>elegans</i>

Doi, Motomichi; Minematsu, Hideki; Kubota, Yukihiko; Nishiwaki, Kiyoji; Miyamoto, Masaaki

doi:10.1242/jcs.138826

Cited by 2 publications

(4 citation statements)

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“…However, not all Vps9 subfamilies are ancient. RIN proteins are capable of binding Ras, and play roles in cell signaling, migration and adhesion, thereby linking Rab5‐mediated endocytosis and cell signaling . In addition to GEF activity for Rab5, RIN proteins are involved in Ras binding, as well as endocytosis of various signalling molecules at the cell surface.…”

Section: Resultsmentioning

confidence: 99%

Regulation of early endosomes across eukaryotes: Evolution and functional homology of Vps9 proteins

Herman

Ali

Field

et al. 2018

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Endocytosis is a crucial process in eukaryotic cells. The GTPases Rab 5, 21 and 22 that mediate endocytosis are ancient eukaryotic features and all available evidence suggests retained conserved function. In animals and fungi, these GTPases are regulated in part by proteins possessing Vps9 domains. However, the diversity, evolution and functions of Vps9 proteins beyond animals or fungi are poorly explored. Here we report a comprehensive analysis of the Vps9 family of GTPase regulators, combining molecular evolutionary data with functional characterization in the non‐opisthokont model organism Trypanosoma brucei. At least 3 subfamilies, Alsin, Varp and Rabex5 + GAPVD1, are found across eukaryotes, suggesting that all are ancient features of regulation of endocytic Rab protein function. There are examples of lineage‐specific Vps9 subfamily member expansions and novel domain combinations, suggesting diversity in precise regulatory mechanisms between individual lineages. Characterization of the Rabex5 + GAPVD1 and Alsin orthologues in T. brucei demonstrates that both proteins are involved in endocytosis, and that simultaneous knockdown prevents membrane recruitment of Rab5 and Rab21, indicating conservation of function. These data demonstrate that, for the Vps9‐domain family at least, modulation of Rab function is mediated by evolutionarily conserved protein‐protein interactions.

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Section: Resultsmentioning

confidence: 99%

Regulation of early endosomes across eukaryotes: Evolution and functional homology of Vps9 proteins

Herman

Ali

Field

et al. 2018

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“…Three putative RAB-5-GEF proteins (RIN-1, RABX-5, and RME-6) are encoded in the genome of C. elegans (Poteryaev et al, 2010;Sato et al, 2005). However, RIN-1 specifically interacts with the GTP-bound form of CED-10/Rac1 (Doi et al, 2013). Therefore, we chose to assay the distributions of RABX-5 and RME-6.…”

Section: Let-502 Interacts With Rabx-5/rab-5-gef and Is Required For The Endosomal Localization Of Rabx-5mentioning

confidence: 99%

“…Likewise, TBC-2 is required for the downregulation of RAB-5 activity during dense core vesicle sorting and releasing in neurons (Chotard et al, 2010b;Sasidharan et al, 2012). The C. elegans genome encodes three putative RAB-5-GEF proteins (Horiuchi et al, 1997), including RIN-1, RABX-5, and RME-6 (Doi et al, 2013;Poteryaev et al, 2010;Sato et al, 2005). Although the mammalian homolog of RIN-1, Rin1, functions as a GEF for Rab5, RIN-1 specifically interacts with the GTP-bound form of CED-10/Rac1 and directs actin remodeling (Doi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…The C. elegans genome encodes three putative RAB-5-GEF proteins (Horiuchi et al, 1997), including RIN-1, RABX-5, and RME-6 (Doi et al, 2013;Poteryaev et al, 2010;Sato et al, 2005). Although the mammalian homolog of RIN-1, Rin1, functions as a GEF for Rab5, RIN-1 specifically interacts with the GTP-bound form of CED-10/Rac1 and directs actin remodeling (Doi et al, 2013). RME-6 has been documented to reside in clathrin-coated vesicles and promote endocytosis in oocytes and coelomocytes (Sato et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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LET-502/ROCK Regulates Endocytic Recycling by Promoting Activation of RAB-5 in a Distinct Subpopulation of Sorting Endosomes

et al. 2020

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The novel Rac effector RIN-1 regulates neuronal cell migration and axon pathfinding in C. elegans

Cited by 2 publications

References 1 publication

Regulation of early endosomes across eukaryotes: Evolution and functional homology of Vps9 proteins

Regulation of early endosomes across eukaryotes: Evolution and functional homology of Vps9 proteins

LET-502/ROCK Regulates Endocytic Recycling by Promoting Activation of RAB-5 in a Distinct Subpopulation of Sorting Endosomes

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