Characterization of the novel human transmembrane protein 9 (TMEM9) that localizes to lysosomes and late endosomes

Kveine, Marit; Tenstad, Ellen; Døsen, Guri; Funderud, Steinar; Rian, Edith

doi:10.1016/s0006-291x(02)02228-3

Cited by 19 publications

(12 citation statements)

References 68 publications

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“…The lack of adequate reagents precluded an analysis of the subcellular localization of endogenous TMEM9B, but a stable low expressing clone of a TMEM9B-EGFP fusion could be used. With this caveat, our data on TMEM9B are reminiscent of the subcellular localization of TMEM9, the closest homolog of TMEM9B, which can be found in lysosomes and late endosomes when overexpressed in COS cells (10). The function of TMEM9, however, is unknown, although a role in intracellular transport was suggested.…”

Section: Discussionmentioning

confidence: 88%

The Lysosomal Transmembrane Protein 9B Regulates the Activity of Inflammatory Signaling Pathways

Dodeller

Gottar

Huesken

et al. 2008

Journal of Biological Chemistry

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The intracellular signaling pathway by which tumor necrosis factor (TNF) induces its pleiotropic actions is well characterized and includes unique components as well as modules shared with other signaling pathways. In addition to the currently known key effectors, further molecules may however modulate the biological response to TNF. In our attempt to characterize novel regulators of the TNF signaling cascade, we have identified transmembrane protein 9B (TMEM9B, c11orf15) as an important component of TNF signaling and a module shared with the interleukin 1␤ (IL-1␤) and Toll-like receptor (TLR) pathways. TMEM9B is a glycosylated protein localized in membranes of the lysosome and partially in early endosomes. The expression of TMEM9B is required for the production of proinflammatory cytokines induced by TNF, IL-1␤, and TLR ligands but not for apoptotic cell death triggered by TNF or Fas ligand. TMEM9B is essential in TNF activation of both the NF-B and MAPK pathways. It acts downstream of RIP1 and upstream of the MAPK and IB kinases at the level of the TAK1 complex. These findings indicate that TMEM9B is a key component of inflammatory signaling pathways and suggest that endosomal or lysosomal compartments regulate these pathways. Tumor necrosis factor (TNF)2 is a pleiotropic mediator of a wide range of cellular responses to infection, such as cytokine and chemokine production, cell migration, cell death, and cell differentiation and maturation (1). TNF plays a pivotal role in several autoimmune disorders such as rheumatoid arthritis; this is underscored by the clinical success of neutralizing TNF with antibodies or soluble receptors (2). A better understanding of intracellular TNF signaling is therefore of high clinical relevance.The two TNF receptors, TNFR1 (p55, TNFRSF1A) and TNFR2 (p75, TNFRSF1B), show high homology in their extracellular domains but less in their intracellular domains. Although soluble TNF binds TNFR1 with higher affinity than TNFR2 and therefore acts primarily via TNFR1, membranebound TNF activates equally TNFR1 and TNFR2 (3). In most tissues TNF signaling is mediated by TNFR1, whereas TNFR2 is restricted to fewer specific tissues, mostly of an immunological nature (3). Upon ligand binding, TNFR1 trimerizes and recruits TNF receptor-associated death domain protein (TRADD), receptor-interacting protein 1 (RIP1), and TNF receptor-associated factor 2 (TRAF2). This first complex acts as a platform at the plasma membrane to activate the NF-B and MAPK signaling cascades, promoting cell survival and the expression of inflammatory cytokines. In a second step, TNFR1 is internalized into endocytic vesicles together with TRADD and RIP1 and recruits the proapoptotic molecules Fas-associated death domain (FADD) and caspase-8. This complex will initiate the apoptotic cell death program if concurrent anti-apoptotic NF-B activation is absent (4).The TGF␤-activated kinase 1 (TAK1) complex has a central function in many inflammatory pathways such as the TNFR, interleukin 1␤ receptor (IL-1R), and several Toll-...

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Section: Discussionmentioning

confidence: 88%

The Lysosomal Transmembrane Protein 9B Regulates the Activity of Inflammatory Signaling Pathways

Dodeller

Gottar

Huesken

et al. 2008

Journal of Biological Chemistry

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“…However, the respective patient was anti-TMEM9B-and ANCA-seronegative, which reflects localized WG [18] and might be suggestive of an autoimmune response limited to the inflamed tissue. TMEM9B is closely related to TMEM9, which is a widely expressed glycosylated transmembrane protein [19]. TMEM9B is an intracellular membrane protein mainly localized in the lysosome and, similar to TMEM9, co-localises with the lysosome-associated membrane protein 1.…”

Section: Resultsmentioning

confidence: 99%

Wegener’s granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin

Thurner

Müller

Cérutti

et al. 2011

Journal of Autoimmunity

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“…The highest two correlates of the Tubb3-network were Rab15 and Rab4b , two G-proteins that are known to play an important role in endosome formation and vesicle movement along actin and tubulin networks (Zuk and Elferink, 2000 ; Falk et al, 2014 ). Several other genes in this list were associated with intracellular trafficking, such as sorting nexin 32 ( Snx32 , a molecule that links transport vesicles to dynactin (Wassmer et al, 2009 ), vesicle associated membrane protein 1 ( Vamp1 , a SNARE protein important for linking vesicles to the target membrane; Hasan et al, 2010 ), Pigu (a GPI anchor protein; Guo et al, 2004 ), and Tmem9 (part of the lysosomal membrane; Kveine et al, 2002 ). These genes were highly correlated with and specific to the Tubb3 -network.…”

Section: Discussionmentioning

confidence: 99%

Genetic Networks in Mouse Retinal Ganglion Cells

et al. 2016

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Retinal ganglion cells (RGCs) are the output neuron of the eye, transmitting visual information from the retina through the optic nerve to the brain. The importance of RGCs for vision is demonstrated in blinding diseases where RGCs are lost, such as in glaucoma or after optic nerve injury. In the present study, we hypothesize that normal RGC function is transcriptionally regulated. To test our hypothesis, we examine large retinal expression microarray datasets from recombinant inbred mouse strains in GeneNetwork and define transcriptional networks of RGCs and their subtypes. Two major and functionally distinct transcriptional networks centering around Thy1 and Tubb3 (Class III beta-tubulin) were identified. Each network is independently regulated and modulated by unique genomic loci. Meta-analysis of publically available data confirms that RGC subtypes are differentially susceptible to death, with alpha-RGCs and intrinsically photosensitive RGCs (ipRGCs) being less sensitive to cell death than other RGC subtypes in a mouse model of glaucoma.

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Characterization of the novel human transmembrane protein 9 (TMEM9) that localizes to lysosomes and late endosomes

Cited by 19 publications

References 68 publications

The Lysosomal Transmembrane Protein 9B Regulates the Activity of Inflammatory Signaling Pathways

The Lysosomal Transmembrane Protein 9B Regulates the Activity of Inflammatory Signaling Pathways

Wegener’s granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin

Genetic Networks in Mouse Retinal Ganglion Cells

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