WIP/ITSN1 complex is involved in cellular vesicle trafficking and formation of filopodia-like protrusions

Gryaznova, T. A.; Gubar, Olga; Burdyniuk, Mariia; Kropyvko, S. V.; Rynditch, A. V.

doi:10.1016/j.gene.2018.06.078

Cited by 16 publications

(11 citation statements)

References 52 publications

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“…S7H,I). Gryaznova et al have reported that WIP also localizes on RAB-4-positive endosomes (Gryaznova et al, 2018). Taken together, these results support that WIP-1 and DBN-1 do not play a profound role during the post-endocytic recycling or degradation pathway.…”

Section: Actin Assembly Cooperate With Dyn-1 For the Scission Of Ccpssupporting

confidence: 62%

“…To our surprise, the wip-1(ok2435)-induced aberrant membranous tubules contained both the CIE cargo hTAC and the CDE cargoes hTfR and MIG-14, and were capped by the CCPs at the tubular tips. Considering that WIP-1 and DBN-1 localize mainly at the CCPs and early endosomes, but not recycling endosomes and late endosomes (Gryaznova et al, 2015;Gryaznova et al, 2018;He et al, 2015), we inferred from the assay of Rhod-Dex staining that these membranous tubules are surface-connected scission-defective endocytic intermediates. However, we cannot exclude other possibilities, such as the F-actin dynamic assembly regulated by WIP-1 and DBN-1 at the early endosomes having an effect on the post-endocytic protein sorting or loss of WIP-1 or DBN-1 resulting in shunting of the CDE cargoes into RME-1-associated tubular subplasmalemma recycling endosomes as the CIE cargoes.…”

Section: Discussionmentioning

confidence: 99%

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WIP-1 and DBN-1 promote scission of endocytic vesicles by bridging actin and Dynamin-1 in theC. elegansintestine

Shi

Duan

Lin

et al. 2019

Journal of Cell Science

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There has been a consensus that actin plays an important role in scission of the clathrin-coated pits (CCPs) together with large GTPases of the dynamin family in metazoan cells. However, the recruitment, regulation and functional interdependence of actin and dynamin during this process remain inadequately understood. Here, based on small-scale screening and in vivo live-imaging techniques, we identified a novel set of molecules underlying CCP scission in the multicellular organism Caenorhabditis elegans. We found that loss of Wiskott−Aldrich syndrome protein (WASP)-interacting protein (WIP-1) impaired CCP scission in a manner that is independent of the C. elegans homolog of WASP/N-WASP (WSP-1) and is mediated by direct binding to G-actin. Moreover, the cortactin-binding domain of WIP-1 serves as the binding interface for DBN-1 (also known in other organisms as Abp1), another actin-binding protein. We demonstrate that the interaction between DBN-1 and F-actin is essential for Dynamin-1 (DYN-1) recruitment at endocytic sites. In addition, the recycling regulator RME-1, a homolog of mammalian Eps15 homology (EH) domain-containing proteins, is increasingly recruited at the arrested endocytic intermediates induced by F-actin loss or DYN-1 inactivation, which further stabilizes the tubular endocytic intermediates. Our study provides new insights into the molecular network underlying F-actin participation in the scission of CCPs. This article has an associated First Person interview with the first author of the paper.

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Section: Actin Assembly Cooperate With Dyn-1 For the Scission Of Ccpssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

WIP-1 and DBN-1 promote scission of endocytic vesicles by bridging actin and Dynamin-1 in theC. elegansintestine

Shi

Duan

Lin

et al. 2019

Journal of Cell Science

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“…Both Rabaptin-5 and KIF16B coordinate Rab5 and Rab4 for efficient vesicle recycling (Hoepfner et al, 2005;Pagano et al, 2004;Stenmark et al, 1995). Recently, ITSN1-S has been reported to localize to Rab4-positive vesicles (Gryaznova et al, 2018) and to interact with DENND2B, an exchange factor for Rab13 involved in EGF receptor recycling (Ioannou et al, 2017). ITSN1 knock-out mice showed only minor (Yu et al, 2008) or no defects (Sakaba et al, 2013) in CME-dependent synaptic vesicle recycling in neurons, but neurons have enlarged EEA1-endosomes (Yu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways

Gubar

Croisé

Kropyvko

et al. 2020

Journal of Cell Science

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Rho GTPases play a key role in various membrane trafficking processes. RhoU is an atypical small Rho GTPase related to Rac/Cdc42, which possesses unique N- and C-terminal domains that regulate its function and its subcellular localization. RhoU localizes at the plasma membrane, on endosomes and in cell adhesion structures where it governs cell signaling, differentiation and migration. However, despite its endomembrane localization, RhoU function in vesicular trafficking has been unexplored. Here, we identified intersectins (ITSNs) as new binding partners for RhoU and showed that the second PxxP motif at the N terminus of RhoU mediated interactions with the SH3 domains of ITSNs. To evaluate the function of RhoU and ITSNs in vesicular trafficking, we used fluorescent transferrin as a cargo for uptake experiments. We showed that silencing of either RhoU or ITSN2, but not ITSN1, increased transferrin accumulation in early endosomes, resulting from a defect in fast vesicle recycling. Concomitantly, RhoU and ITSN2 colocalized to a subset of Rab4-positive vesicles, suggesting that a RhoU–ITSN2 interaction may occur on fast recycling endosomes to regulate the fate of vesicular cargos.

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“…21 The lack of intracellular DNA caused by ITSN1 knockout alters the signal balance of Smad2/3-ERK1/2 downstream of transferring growth factor receptor I, which causes the proliferation and neovascularization of pulmonary endothelial cells. 21,22 Thus, we decided to investigate the role of ITSN in breast carcinoma. Our results showed that ITSN1 had no connection with poor survival (Figure 6), which could be caused by small sample size.…”

Section: Discussionmentioning

confidence: 99%

<p>Intersectin 1 (ITSN1) identified by comprehensive bioinformatic analysis and experimental validation as a key candidate biological target in breast cancer</p>

Xie¹,

Xiong²,

Li³

et al. 2019

OTT

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Background: As one of the most common cancers, breast carcinoma is the most common disease in women. Intersectin 1 (ITSN1) contributes to the actin cytoskeleton reconstruction in breast cancer. Purpose: The objective of this study to explore the functions of ITSN1 in breast carcinoma. Methods: We downloaded microarray datasets GSE8087, GSE50697, and GSE98238 from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were used to construct a protein-protein interaction (PPI) network using STRING database, and the modules from PPI network were verified by Cytoscape software. Gene ontology terms and Kyoto Encyclopedia of Gene and Genome pathway were used to analyze the biological functions using the DAVID database. ONCOMINE, GEPIA, UALCAN, and Human Protein Atlas databases were used to investigate the characteristics of ITSN1 for the prognosis of breast carcinoma. Cell counting kit-8, flow cytometry, and colony formation assays were used to detect cell viability, cell apoptosis, and cell proliferation. RT-PCR and Western blot assays were used to detect ITSN1, Ki67, and cleaved caspase-3 expressions. Results: Low expressions of ITSN1 were significantly associated with clinical cancer stages. RT-PCR and Western blot analysis showed low expression of ITSN1 in breast cancer tissues and cell lines. ITSN1 inhibition could promote cell proliferation and inhibit cell apoptosis, while ITSN1 overexpression could inhibit cell proliferation and increase cell apoptosis by regulating the levels of expression of Ki67 and cleaved-caspase-3. Conclusion: The results indicated that ITSN1 could be a prognostic biomarker for survivals of breast cancer patients.

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WIP/ITSN1 complex is involved in cellular vesicle trafficking and formation of filopodia-like protrusions

Cited by 16 publications

References 52 publications

WIP-1 and DBN-1 promote scission of endocytic vesicles by bridging actin and Dynamin-1 in theC. elegansintestine

WIP-1 and DBN-1 promote scission of endocytic vesicles by bridging actin and Dynamin-1 in theC. elegansintestine

The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways

<p>Intersectin 1 (ITSN1) identified by comprehensive bioinformatic analysis and experimental validation as a key candidate biological target in breast cancer</p>

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