TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7

Zhang, Xiangming; Walsh, Bong; Mitchell, Christina A.; Rowe, Tony

doi:10.1016/j.bbrc.2005.07.070

Cited by 93 publications

(99 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunofluorescence microscopy using specific antibodies against a recombinant TBC1D15 fragment (amino acid residues 1-333) revealed staining of the cytoplasm, as reported previously (Zhang et al, 2005), as well as mitochondrial network structures ( Fig. 2A), demonstrating that endogenously expressed TBC1D15 localizes to both the mitochondria and cytoplasm in HeLa cells.…”

Section: Fis1 Stimulates Mitochondrial Localization Of Tbc1d15supporting

confidence: 85%

“…TBC1D15 homologues have higher sequence similarity among vertebrates (72% homology between human and Xenopus laevis), than with the fruit fly, nematodes, and yeast (D. melanogaster, 46%; Caenorhabditis elegans, 49%; and Saccharomyces cerevisiae, 40%). Human TBC family member TBC1D17 shares a high amino acid similarity with TBC1D15 (50% overall identity; (Zhang et al, 2005), although its RNAi in HeLa cells had no obvious effect on mitochondrial morphology (data not shown). The outcome of double TBC1D15 and TBC1D17 RNAi was indistinguishable from that of TBC1D15 alone (data not shown), suggesting that TBC1D15 plays a major role in mitochondrial morphology in HeLa cells.…”

Section: Tbc Domain-containing Proteins and Mitochondrial Morphologymentioning

confidence: 96%

“…7). TBC1D15 was reported to function in lysosome/endosome fusion as a putative GTPase regulator for Rab7 and Rab11 in mammalian cells (Peralta et al, 2010;Zhang et al, 2005). However, the specificity of TBC proteins for Rab proteins is often promiscuous and they have been demonstrated to have multiple functions (Fukuda, 2011).…”

Section: Tbc Domain-containing Proteins and Mitochondrial Morphologymentioning

confidence: 99%

See 2 more Smart Citations

Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology

Onoue

Jofuku

Ban-Ishihara

et al. 2013

Journal of Cell Science

127

124

View full text Add to dashboard Cite

SummaryIn yeast, C-tail-anchored mitochondrial outer membrane protein Fis1 recruits the mitochondrial-fission-regulating GTPase Dnm1 to mitochondrial fission sites. However, the function of its mammalian homologue remains enigmatic because it has been reported to be dispensable for the mitochondrial recruitment of Drp1, a mammalian homologue of Dnm1. We identified TBC1D15 as a Fis1-binding protein in HeLa cell extracts. Immunoprecipitation revealed that Fis1 efficiently interacts with TBC1D15 but not with Drp1. Bacterially expressed Fis1 and TBC1D15 formed a direct and stable complex. Exogenously expressed TBC1D15 localized mainly in cytoplasm in HeLa cells, but when coexpressed with Fis1 it localized to mitochondria. Knockdown of TBC1D15 induced highly developed mitochondrial network structures similar to the effect of Fis1 knockdown, suggesting that the TBC1D15 and Fis1 are associated with the regulation of mitochondrial morphology independently of Drp1. These data suggest that Fis1 acts as a mitochondrial receptor in the recruitment of mitochondrial morphology protein in mammalian cells.

show abstract

Section: Fis1 Stimulates Mitochondrial Localization Of Tbc1d15supporting

confidence: 85%

Section: Tbc Domain-containing Proteins and Mitochondrial Morphologymentioning

confidence: 96%

Section: Tbc Domain-containing Proteins and Mitochondrial Morphologymentioning

confidence: 99%

See 1 more Smart Citation

Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology

Onoue

Jofuku

Ban-Ishihara

et al. 2013

Journal of Cell Science

127

124

View full text Add to dashboard Cite

show abstract

“…The nucleotide cycle of this Rab is regulated by the GTPase-activating proteins (GAPs) TBC1D15 (Zhang et al, 2005) and TBC1D2 (also known as Armus) (Frasa et al, 2010), and the GEF complex Mon1-Ccz1 (Nordmann et al, 2010). The homotypic fusion and protein sorting (HOPS) complex functions as a Rab7 GEF in yeast (Wurmser et al, 2000), and overexpression of some of the HOPS subunits causes perinuclear clustering of lysosomes in mammalian cells (Wurmser et al, 2000;Poupon et al, 2003).…”

Section: Retrograde Transportmentioning

confidence: 99%

Mechanisms and functions of lysosome positioning

Guardia

Keren-Kaplan

et al. 2016

Journal of Cell Science

461

466

View full text Add to dashboard Cite

Lysosomes have been classically considered terminal degradative organelles, but in recent years they have been found to participate in many other cellular processes, including killing of intracellular pathogens, antigen presentation, plasma membrane repair, cell adhesion and migration, tumor invasion and metastasis, apoptotic cell death, metabolic signaling and gene regulation. In addition, lysosome dysfunction has been shown to underlie not only rare lysosome storage disorders but also more common diseases, such as cancer and neurodegeneration. The involvement of lysosomes in most of these processes is now known to depend on the ability of lysosomes to move throughout the cytoplasm. Here, we review recent findings on the mechanisms that mediate the motility and positioning of lysosomes, and the importance of lysosome dynamics for cell physiology and pathology.

show abstract

“…In some cases, TBC-containing proteins act as GAPs (GTPase-activating proteins) for RABs, with the TBC domain encoding the catalytic activity (Cuif et al, 1999;Lanzetti et al, 2000;Haas et al, 2005;Miinea et al, 2005;Zhang et al, 2005). It is not clear, however, whether all TBC-containing proteins display similar activity.…”

Section: Introductionmentioning

confidence: 99%

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Frittoli

Palamidessi

Pizzigoni

et al. 2008

MBoC

View full text Add to dashboard Cite

The generation of novel genes and proteins throughout evolution has been proposed to occur as a result of whole genome and gene duplications, exon shuffling, and retrotransposition events. The analysis of such genes might thus shed light into the functional complexity associated with highly evolved species. One such case is represented by TBC1D3, a primatespecific gene, harboring a TBC domain. Because TBC domains encode Rab-specific GAP activities, TBC-containing proteins are predicted to play a major role in endocytosis and intracellular traffic. Here, we show that the TBC1D3 gene originated late in evolution, likely through a duplication of the RNTRE locus, and underwent gene amplification during primate speciation. Despite possessing a TBC domain, TBC1D3 is apparently devoid of Rab-GAP activity. However, TBC1D3 regulates the optimal rate of epidermal growth factor-mediated macropinocytosis by participating in a novel pathway involving ARF6 and RAB5. In addition, TBC1D3 binds and colocalize to GGA3, an ARF6-effector, in an ARF6-dependent manner, and synergize with it in promoting macropinocytosis, suggesting that the two proteins act together in this process. Accordingly, GGA3 siRNA-mediated ablation impaired TBC1D3-induced macropinocytosis. We thus uncover a novel signaling pathway that appeared after primate speciation. Within this pathway, a TBC1D3:GGA3 complex contributes to optimal propagation of signals, ultimately facilitating the macropinocytic process. INTRODUCTIONGene duplication, exon shuffling, and retrotransposition events played crucial roles during vertebrate evolution (Long, 2001;McLysaght et al., 2002;Brosius, 2003). About 5% of the human genome is composed of duplicated segments that emerged during the past 35 million years of primate evolution, resulting in the generation of novel protein functions (Courseaux and Nahon, 2001;Taylor and Raes, 2004).One of the cellular processes, whose regulation has became more and more complex and tightly regulated during evolution is endocytosis. Endocytosis serves to maintain cellular and organismal homeostasis by mediating the uptake of fluids, solutes, and signaling molecules and their receptors. Multiple mechanisms of endocytosis operate within a single cell (Conner and Schmid, 2003). Among them, two major categories are phagocytosis and pinocytosis, which mediate the uptake of particles or of fluid, respectively (Conner and Schmid, 2003).Pinocytosis encompasses a variety of different membraneentry routes and is invariably characterized by the relatively small size (50 -150 nm) of the internalized particles. Large volumes of fluid are, instead, engulfed by extension, folding, and closure of plasma membranes (PM) through a process termed macropinocytosis (Swanson and Watts, 1995). Macropinocytosis displays many similarities to phagocytosis; the biochemical and cellular components of these endocytic mechanisms have been best characterized in hematopoietic cells, in processes such as phagocytosis by macrophages in response to Fc receptor stimulation, or ma...

show abstract

TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7

Cited by 93 publications

References 31 publications

Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology

Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology

Mechanisms and functions of lysosome positioning

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Contact Info

Product

Resources

About