The Sorting Nexin, DSH3PX1, Connects the Axonal Guidance Receptor, Dscam, to the Actin Cytoskeleton

Worby, Carolyn A.; Simonson-Leff, Nancy; Clemens, James C.; Kruger, Robert P.; Muda, Marco; Dixon, Jack E.

doi:10.1074/jbc.m107080200

Cited by 72 publications

(84 citation statements)

References 52 publications

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“…This spatial and temporal heterogeneity, which has also been observed for actin's association with CCPs (Yarar et al, 2005), may reflect a dual role for SNX9 in endocytosis. In this regard, it is interesting that SNX9 has been shown to interact with WASP in Drosophila (Worby et al, 2001). We did not detect gross differences in phalloidin staining of the actin cytoskeleton in control versus SNX9 siRNA-treated cells (unpublished data).…”

Section: Discussionmentioning

confidence: 85%

“…Both have SH3 domains and BAR domains, and both proteins bind dynamin, AP2, clathrin, and lipids. Finally, both have been implicated in regulation of the actin cytoskeleton (Mundigl et al, 1998;Worby et al, 2001). Thus, it has been suggested that SNX9, like amphiphysin, might function as an endocytic scaffold to recruit dynamin to the plasma membrane as CCPs assemble (Lundmark and Carlsson, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…SNX9, also called SH3PX1, has in addition to its PX domain, an SH3 domain, and a BAR (Bin/amphiphysin/Rvs) domain, thought to be involved in lipid binding, curvature sensing, and dimerization (Habermann, 2004;Peter et al, 2004). Like other sorting nexins, SNX9 interacts with several transmembrane proteins including Dscam in Drosophila, the insulin receptor and two metalloprotease disintegrins, MDC5 and MDC15 (Howard et al, 1999;Worby et al, 2001;MaCaulay et al, 2003). SNX9 has also been linked to the actin cytoskeleton through its interaction in Drosophila with the orthologue of WASP (Worby et al, 2001).…”

mentioning

confidence: 99%

“…Like other sorting nexins, SNX9 interacts with several transmembrane proteins including Dscam in Drosophila, the insulin receptor and two metalloprotease disintegrins, MDC5 and MDC15 (Howard et al, 1999;Worby et al, 2001;MaCaulay et al, 2003). SNX9 has also been linked to the actin cytoskeleton through its interaction in Drosophila with the orthologue of WASP (Worby et al, 2001). Finally, several studies have suggested a potential role for SNX9 in clathrin-mediated endocytosis based on its interaction with components of the CME machinery (Lin et al, 2002; Carlsson, 2002, 2003;Miele et al, 2004).…”

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confidence: 99%

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SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

Soulet

Yarar

Leonard

et al. 2005

MBoC

188

233

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Dynamin, a central player in clathrin-mediated endocytosis, interacts with several functionally diverse SH3 domaincontaining proteins. However, the role of these interactions with regard to dynamin function is poorly defined. We have investigated a recently identified protein partner of dynamin, SNX9, sorting nexin 9. SNX9 binds directly to both dynamin-1 and dynamin-2. Moreover by stimulating dynamin assembly, SNX9 stimulates dynamin's basal GTPase activity and potentiates assembly-stimulated GTPase activity on liposomes. In fixed cells, we observe that SNX9 partially localizes to clathrin-coated pits. Using total internal reflection fluorescence microscopy in living cells, we detect a transient burst of EGFP-SNX9 recruitment to clathrin-coated pits that occurs during the late stages of vesicle formation and coincides spatially and temporally with a burst of dynamin-mRFP fluorescence. Transferrin internalization is inhibited in HeLa cells after siRNA-mediated knockdown of SNX9. Thus, our results establish that SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity. INTRODUCTIONThe GTPase dynamin plays a critical role in clathrin-mediated endocytosis (CME; Hinshaw, 2000). Dynamin self-assembles into a collar-like structure around the necks of deeply invaginated clathrin-coated pits (CCPs) where it is believed to directly mediate membrane fission and vesicle release. Dynamin is also associated with newly formed coated pits (Damke et al., 1994;Evergren et al., 2004) where it may function to regulate early stages of coated pit maturation (Sever et al., 2000a;Song and Schmid, 2003;Song et al., 2004).Although only one isoform of dynamin exists in Drosophila and in Caenorhabditis elegans, mammals express at least three isoforms, which are ϳ70% identical to each other. Dynamin-1, the first identified protein in the dynamin family, is expressed exclusively in neuronal cells where it functions in synaptic vesicle recycling (Shpetner and Vallee, 1989;Nakata et al., 1991;Sontag et al., 1994). Dynamin-2 is ubiquitously expressed (Cook et al., 1994;Sontag et al., 1994) and localizes to endocytic CCPs where it functions, like dynamin-1, in endocytosis (Damke et al., 1994;Altschuler et al., 1998). However, dynamin-2 may also be involved in vesicle formation at the Golgi Kreitzer et al., 2000), in regulating actin dynamics (Schafer, 2004), in cell signaling (Kranenburg et al., 1999;Fish et al., 2000), and has recently been localized to the centriole (Thompson et al., 2004). Dynamin-3, which is most highly expressed in testis but also detectable in neurons (Gray et al., 2003) and in lung (Nakata et al., 1993), has been less well studied.Dynamins are atypical GTPases, distinguished by their large size, low affinity for GTP, and high intrinsic rates of GTP hydrolysis (Sever et al., 2000b;Song and Schmid, 2003). Moreover, dynamin can self-assemble in solution (Hinshaw and Schmid, 1995) or on liposome templates into rings and spiral-like structures (Stowell et al., 199...

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

Soulet

Yarar

Leonard

et al. 2005

MBoC

188

233

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“…Drosophila does not have DNA rearrangements that occur during immune cell development in humans. However, the Drosophila immune system utilizes alternative splicing of the Ig-domain protein DSCAM which has over 18,000 alternative-splice isoforms (Schmucker et al, 2000;Schmucker and Flanagan, 2004;Watson et al, 2005;Worby et al, 2001). All in all, there are likely well over 100,000 protein products in both humans and Drosophila, but the precise numbers are not yet known.…”

Section: Microarrays and Nutrition Studies In Microarrays And Nutritimentioning

confidence: 99%

Evolutionary conservation of metabolism explains howDrosophila nutrigenomics can help us understand human nutrigenomics

Ruden

2006

Genes Nutr

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Expression of sorting nexin 12 is regulated in developing cerebral cortical neurons

Mizutani

Nakamura

Kato

et al. 2011

J of Neuroscience Research

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The sorting nexins (SNXs) are a family of proteins functioning in diverse processes, including endocytosis, endosomal sorting, and endosomal signaling. Sorting nexin 12 (SNX12) is one of the SNXs family members; however, its function remains unknown. To clarify the function of SNX12, in this study, we first investigated the expression profiles in mice, particularly in the central nervous system (CNS), and then analyzed the functional role on neurite outgrowth. We found that SNX12 was widely expressed in the adult mouse CNS and that its expression level was higher in the cerebral cortex than in other examined regions. SNX12 expression was detected in the neurons but not the glial cells of the adult mouse cerebral cortex. In the fetal brain, SNX12 expression increased during the embryonic stage and gradually decreased after birth. Although the immunoreactivities of SNX12 were widespread in the cerebral cortical cells in the fetal brain, the immunopositive signals of SNX12 were more intense in the postmitotic neurons in the cortical plate than in the proliferating precursor cells in the ventricular zone, suggesting that SNX12 plays critical roles in the postmitotic neurons during cerebral cortical development. Furthermore, in mouse neuroblastoma and N1E-115 cells and rat primary cortical neurons, SNX12 expression was increased as neurite outgrowth progressed and the knockdown of SNX12 attenuated the outgrowth of neurites. These results suggest that SNX12 regulates neurite formation during cerebral cortical development.

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The Sorting Nexin, DSH3PX1, Connects the Axonal Guidance Receptor, Dscam, to the Actin Cytoskeleton

Abstract: Dock, an adaptor protein that functions in

Cited by 72 publications

References 52 publications

SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

Evolutionary conservation of metabolism explains howDrosophila nutrigenomics can help us understand human nutrigenomics

Expression of sorting nexin 12 is regulated in developing cerebral cortical neurons

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