Assembly of Urothelial Plaques: Tetraspanin Function in Membrane Protein Trafficking

Hu, Chih‐Chi Andrew; Liang, Feng; Zhou, Ge; Tu, Liyu; Tang, Chih-Hang Anthony; Zhou, Jessica; Kreibich, Gert; Sun, Tung‐Tien

doi:10.1091/mbc.e05-02-0136

Cited by 102 publications

(155 citation statements)

References 48 publications

(57 reference statements)

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“…4). Early associations with partners during biosynthesis of tetraspanins have previously been demonstrated for the pairing of uroplakins (11,22,51) and for the association of CD151 with integrin ␣3 (23). Our findings support the proposition that tetraspanin web assembly is initiated in the ER, where the tetraspanin-partner building blocks are first formed, and then the web is further assembled with other tetraspanins and their partners during intracellular processing in the Golgi (25,58).…”

Section: Discussionmentioning

confidence: 94%

Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments

Shoham

Rajapaksa

Kuo

et al. 2006

Molecular and Cellular Biology

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The tetraspanin web is composed of a network of tetraspanins and their partner proteins that facilitate cellular interactions and fusion events by an unknown mechanism. Our aim was to unravel the web partnership between the tetraspanin CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that CD81 plays multiple roles in the processing, intracellular trafficking, and membrane functions of CD19. Surprisingly, these different roles are embodied in distinct CD81 domains, which function in the different cellular compartments: the N-terminal tail of CD81 has an effect on the glycosylation of CD19; the first transmembrane domain of CD81 is sufficient to support the exit of CD19 from the endoplasmic reticulum, although the large extracellular loop (LEL) of CD81 associates physically with CD19 early during biosynthesis; and finally, the TM2 and TM3 domains of CD81 play a role in the transmission of signals initiated upon engagement of the LEL. The participation of distinct CD81 domains in varied functions may explain the pleiotropic effects of CD81 within the tetraspanin web.

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Section: Discussionmentioning

confidence: 94%

Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments

Shoham

Rajapaksa

Kuo

et al. 2006

Molecular and Cellular Biology

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“…Tetraspanins have been reported to function through interaction with other membrane proteins, including cytokine receptors, to regulate the downstream signaling transduction, 12,28 whereas the CD9-binding partner on cell surface of GSCs has not been defined. To identify the CD9-interacting proteins in GSCs, we transduced GSCs with a Flag-tagged CD9, and the CD9 associated protein complex was then immunoprecipitated with anti-Flag antibody followed by MS analyses.…”

Section: Resultsmentioning

confidence: 99%

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

et al. 2016

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Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the prosurvival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitindependent lysosomal degradation to facilitate the STAT3 activation in GSCs. CD9 is preferentially expressed in GSCs of human GBM tumors. Mass spectrometry analysis identified gp130 as an interacting protein of CD9 in GSCs, which was confirmed by immunoprecipitation and immunofluorescent analyses. Disrupting CD9 or gp130 by shRNA significantly inhibited the self-renewal and promoted the differentiation of GSCs. Moreover, CD9 disruption markedly reduced gp130 protein levels and STAT3 activating phosphorylation in GSCs. CD9 stabilized gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote the BMX-STAT3 signaling in GSCs. Importantly, targeting CD9 potently inhibited GSC tumor growth in vivo, while ectopic expression of the constitutively activated STAT3 (STAT3-C) restored the tumor growth impaired by CD9 disruption. Collectively, we uncovered a critical regulatory mechanism mediated by tetraspanin CD9 to maintain the stem cell-like property and tumorigenic potential of GSCs.

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“…We began our mutational analysis with UPIIIA, a member of the uroplakin family of proteins that forms the 'asymmetric unit membrane' covering the apical surface of urothelial umbrella cells (31,32). As well as conferring a permeability barrier function to the mature urothelium, the severe renal tract malformations in UPII (33) and UPIIIA (34) null-mutant mice, including obstructed ureters and a malformed vesicoureteric junction respectively, has established a role for uroplakin proteins in development.…”

Section: Discussionmentioning

confidence: 99%

Mutational analyses of UPIIIA, SHH, EFNB2, and HNF1β in persistent cloaca and associated kidney malformations

Jenkins

Bitner‐Glindzicz

Thomasson

et al. 2007

Journal of Pediatric Urology

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Objectives-'Persistent cloaca' is a severe malformation affecting females in which the urinary, genital and alimentary tracts share a single conduit. Previously, a Uroplakin IIIA (UPIIIA) mutation was reported in one individual with persistent cloaca, and UPIIIA, Sonic Hedgehog (SHH), Ephrin B2 (EFNB2) and Hepatocyte Nuclear Factor 1β (HNF1β) are expressed during the normal development of organs that are affected in this condition. HNF1β mutations have been associated with uterine malformations in humans, and mutations of genes homologous to human SHH or EFNB2 cause persistent cloaca in mice.Patients and Methods-We sought mutations of coding regions of UPIIIA, SHH, EFNB2 and HNF1β genes by direct sequencing in a group of 20 patients with persistent cloaca. Most had associated malformations of the upper renal tract and over half had impaired renal excretory function. The majority of patients had congenital anomalies outside the renal/genital tracts and two had the VACTERL association.Results-Apart from a previously described index case, we failed to find UPIIIA mutations, and no patient had a SHH, EFNB2 or HNF1β mutation.Conclusion-Persistent cloaca is only rarely associated with UPIIIA mutation. Despite the fact that SHH and EFNB2 are appealing candidate genes, based on their expression patterns and mutant mice phenotypes, they were not mutated in these humans with persistent cloaca. Although HNF1β mutations can perturb paramesonephric duct fusion in humans, HNF1β was not mutated in persistent cloaca.

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Assembly of Urothelial Plaques: Tetraspanin Function in Membrane Protein Trafficking

Cited by 102 publications

References 48 publications

Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments

Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

Mutational analyses of UPIIIA, SHH, EFNB2, and HNF1β in persistent cloaca and associated kidney malformations

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