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

Zhang, Wenjuan; Wang, Shimin; Yang, Chao; Hu, Can; Chen, Dan; Luo, Qian; He, Zhen; Liao, Yuhan; Yao, Yuxin; Chen, Juan; He, Jun; Hu, Junbo; Xia, Tian; Lin, Long; Shi, Anbing

doi:10.1016/j.celrep.2020.108173

Cited by 7 publications

(5 citation statements)

References 101 publications

(159 reference statements)

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“…However, the mechanism controlling the localization of SMAPs is still not well understood. Here, by using a well-established in vivo membrane trafficking investigation model ( Chen et al, 2018 ; Chen et al, 2019 ; Gao et al, 2020 ; Zhang et al, 2020 ; Yan et al, 2021 ), we showed that the integrity of AP-1 adaptor is necessary for the TGN positioning of SMAP-1. Although we did not specifically identify which AP-1 subunit governs the TGN localization of SMAP-1, our results suggested that in addition to CALM, SMAP-1 underlies an additional clathrin assembly mechanism, enriching the understanding of AP-1/clathrin coat assembly.…”

Section: Discussionmentioning

confidence: 89%

AP-1 Recruits SMAP-1/SMAPs to the trans-Golgi Network to Promote Sorting in Polarized Epithelia

Wang

Yao

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Coordinated AP-1 and clathrin coat assembly mediate secretory sorting on the trans-Golgi network (TGN) during conventional secretion. Here we found that SMAP-1/SMAPs deficiency caused the apical protein ERM-1 to accumulate on the basolateral side of the TGN. In contrast, the basolateral protein SLCF-1 appeared abnormally on the apical membrane. SMAP-1 colocalized with AP-1 on the TGN. The integrity of AP-1 is required for the subcellular presence of SMAP-1. Moreover, we found that the loss of SMAP-1 reduced clathrin-positive structures in the cytosol, suggesting that SMAP-1 has a regulatory role in clathrin assembly on the TGN. Functional experiments showed that overexpressing clathrin effectively alleviated exocytic defects due to the lack of SMAP-1, corroborating the role of SMAP-1 in promoting the assembly of clathrin on the TGN. Together, our results suggested that the AP-1 complex regulates the TGN localization of SMAP-1, promoting clathrin assembly to ensure polarized conventional secretion in C. elegans intestinal epithelia.

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Section: Discussionmentioning

confidence: 89%

AP-1 Recruits SMAP-1/SMAPs to the trans-Golgi Network to Promote Sorting in Polarized Epithelia

Wang

Yao

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…Interestingly, three putative Rho effectors, formin CYK-1/mDia, LET-502/ROCK, and RTKN- 1/Rhotekin, are known to function in basolateral recycling in the C. elegans intestine, although current models posit that these proteins function independently of RHO-1 in recycling (11, 54, 55). Branched actin formed by Arp2/3 is traditionally considered the relevant F-actin type associated with endosomes, but recycling may require a balance of branched and linear actin for proper function.…”

Section: Discussionmentioning

confidence: 99%

Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II

Rodriguez-Polanco

Norris

Velasco

et al. 2023

Preprint

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After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F-BAR and SH3 domain Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here we sought to determine the significance of a predicted interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations we engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo, as does loss of the PXF-1 target RAP-1. Rap-GTPases have been shown in several contexts to negatively regulate RhoA activity. Our results show that RHO-1/RhoA is enriched on SDPN-1 and RAP-1 positive endosomes in the C. elegans intestine, and loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well-known for controlling actomyosin contraction cycles, although little is known of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1 positive endosomes, with two non-muscle myosin II heavy chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, while depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating actomyosin contractility in controlling recycling endosome function.

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“…In particular, Rab5 promotes the fusion of nascent endocytic vesicles with early endosomes and fusion between early endosomes, so it is often used as a marker for early endosomes [141] . Studies in various systems have revealed multiple Rab5 GEF proteins, including RABX-5/Rabex-5 [109] , [150] , [149] , [153] , hRME-6/RME-6 [112] , and Rin2/RIN-1 [29] . RABX-5/Rabex-5 is the first protein identified as a small GTPase GEF and is primarily localized at early endosomes [52] .…”

Section: Rab5 Directs Biogenesis and Functions Of Early Endosomesmentioning

confidence: 99%

“…Given that the overactivation of Rab proteins can adversely affect endocytic trafficking, it is crucial for TBC-2, a Rab5/RAB-5 GAP, to shut down RAB-5 activity in a timely manner [22] . Zhang et al found that RAB-5 resides in discrete endosome subpopulations in the intestine of C. elegans , and under the oversight of CED-10, LET-502 synergizes with RABX-5 to revitalize RAB-5 on a subset of endosomes in the deep cytosol, ensuring the progress of basolateral recycling [150] , [149] , [153] . USP6NL/RN-tre is thought to be a GAP shared by Rab5 and Rab41, while TBC1D2/Armus/TBC-2 appears to function primarily as a GAP for Rab7 [22] , [34] .…”

Section: Rab5 Directs Biogenesis and Functions Of Early Endosomesmentioning

confidence: 99%

“…Numerous cancers, including hepatocellular carcinoma, glioma, cervical cancer, osteosarcoma, etc., exhibit high expression of Rab10 [57] , [138] , [47] , [150] , [149] , [153] , which affects the prognosis of tumors and controls the apoptosis, proliferation, migration, invasion, and autophagy processes of tumor cells [155] . In addition, the aberrant phosphorylation of Rab10 may contribute to the altered vesicular transport in Alzheimer's disease.…”

Section: Rab10 Is a Molecular Switch For Polarized Sorting And Recycl...mentioning

confidence: 99%

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Rab GTPases: The principal players in crafting the regulatory landscape of endosomal trafficking

Zhang

Jiang

Shi

2022

Computational and Structural Biotechnology Journal

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

Cited by 7 publications

References 101 publications

AP-1 Recruits SMAP-1/SMAPs to the trans-Golgi Network to Promote Sorting in Polarized Epithelia

AP-1 Recruits SMAP-1/SMAPs to the trans-Golgi Network to Promote Sorting in Polarized Epithelia

Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II

Rab GTPases: The principal players in crafting the regulatory landscape of endosomal trafficking

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