PACSIN2

Summary

Gene Symbol: PACSIN2
Description: protein kinase C and casein kinase substrate in neurons 2
Alias: SDPII, protein kinase C and casein kinase substrate in neurons protein 2, cytoplasmic phosphoprotein PACSIN2, syndapin-2, syndapin-II, syndapin2
Species: human
Products:     PACSIN2

Top Publications

  1. Modregger J, Ritter B, Witter B, Paulsson M, Plomann M. All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis. J Cell Sci. 2000;113 Pt 24:4511-21 pubmed
    ..These characteristics of the PACSIN protein family suggest a general function in recruitment of the interacting proteins to sites of endocytosis. ..
  2. Hansen C, Howard G, Nichols B. Pacsin 2 is recruited to caveolae and functions in caveolar biogenesis. J Cell Sci. 2011;124:2777-85 pubmed publisher
    ..We propose that pacsin 2 has an important role in the formation of plasma membrane caveolae...
  3. Senju Y, Itoh Y, Takano K, Hamada S, Suetsugu S. Essential role of PACSIN2/syndapin-II in caveolae membrane sculpting. J Cell Sci. 2011;124:2032-40 pubmed publisher
    ..Here, we show that the F-BAR protein PACSIN2 sculpts the plasma membrane of the caveola...
  4. Wang Q, Navarro M, Peng G, Molinelli E, Goh S, Judson B, et al. Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein Pacsin/Syndapin. Proc Natl Acad Sci U S A. 2009;106:12700-5 pubmed publisher
    ..The regulated deformation of membranes and promotion of tubule constrictions by Pacsin suggests a more versatile function of these proteins in vesiculation and endocytosis beyond their role as scaffold proteins. ..
  5. Kessels M, Qualmann B. The syndapin protein family: linking membrane trafficking with the cytoskeleton. J Cell Sci. 2004;117:3077-86 pubmed
    ..Given the distinct expression patterns of the different syndapins and their splice forms, these proteins could have isoform-specific functions. ..
  6. de Kreuk B, Nethe M, Fernandez Borja M, Anthony E, Hensbergen P, Deelder A, et al. The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration. J Cell Sci. 2011;124:2375-88 pubmed publisher
    ..Here, we show that Rac1 associates, through its C-terminus, with the F-BAR domain protein PACSIN2, an inducer of membrane tubulation and a regulator of endocytosis...
  7. Popov S, Popova E, Inoue M, Wu Y, Gottlinger H. HIV-1 gag recruits PACSIN2 to promote virus spreading. Proc Natl Acad Sci U S A. 2018;115:7093-7098 pubmed publisher
    ..We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components ..
  8. Lucas E, Reid C, McMeekin L, Dougherty S, Floyd C, Cowell R. Cerebellar transcriptional alterations with Purkinje cell dysfunction and loss in mice lacking PGC-1α. Front Cell Neurosci. 2014;8:441 pubmed publisher
    ..We found significant reductions in transcripts with synaptic (complexin1, Cplx1; Pacsin2), structural (neurofilament heavy chain, Nefh), and metabolic (isocitrate dehydrogenase 3a, Idh3a; neutral ..
  9. Kostan J, Salzer U, Orlova A, Törö I, Hodnik V, Senju Y, et al. Direct interaction of actin filaments with F-BAR protein pacsin2. EMBO Rep. 2014;15:1154-62 pubmed publisher
    ..Here, we show that the F-BAR domain protein pacsin2 is able to associate with actin filaments using the same concave surface employed to bind to membranes, while ..

More Information

Publications37

  1. Dumont V, Tolvanen T, Kuusela S, Wang H, Nyman T, Lindfors S, et al. PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease. FASEB J. 2017;31:3978-3990 pubmed publisher
    ..Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD...
  2. Dorland Y, Malinova T, van Stalborch A, Grieve A, van Geemen D, Jansen N, et al. The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions. Nat Commun. 2016;7:12210 pubmed publisher
    ..Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion...
  3. Krawczyk K, Yao Mattisson I, Ekman M, Oskolkov N, Grantinge R, Kotowska D, et al. Myocardin Family Members Drive Formation of Caveolae. PLoS ONE. 2015;10:e0133931 pubmed publisher
    ..b>PACSIN2 also increased, establishing positive regulation of caveolae genes from three families...
  4. Eicher J, Chami N, Kacprowski T, Nomura A, Chen M, Yanek L, et al. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals. Am J Hum Genet. 2016;99:40-55 pubmed publisher
    ..rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants...
  5. Billcliff P, Noakes C, Mehta Z, Yan G, Mak L, Woscholski R, et al. OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates. Mol Biol Cell. 2016;27:90-107 pubmed publisher
    ..Our data indicate a role for OCRL1, via IPIP27A, in regulating the formation of pacsin 2-dependent trafficking intermediates and reveal a mechanism for coupling PtdIns(4,5)P2 hydrolysis with carrier biogenesis on endomembranes. ..
  6. Ludwig A, Howard G, Mendoza Topaz C, Deerinck T, Mackey M, Sandin S, et al. Molecular composition and ultrastructure of the caveolar coat complex. PLoS Biol. 2013;11:e1001640 pubmed publisher
    ..3D electron tomograms of the caveolar coat, labeled using cavin-MiniSOG, show that the caveolar coat is composed of repeating units of a unitary caveolar coat complex. ..
  7. Stocco G, Yang W, Crews K, Thierfelder W, Decorti G, Londero M, et al. PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Hum Mol Genet. 2012;21:4793-804 pubmed publisher
    ..associated with TPMT activity in HapMap cell lines was protein kinase C and casein kinase substrate in neurons 2 (PACSIN2)...
  8. Kim S, Cheng Y, Hsu F, Jin T, Kader A, Zheng S, et al. Prostate cancer risk-associated variants reported from genome-wide association studies: meta-analysis and their contribution to genetic Variation. Prostate. 2010;70:1729-38 pubmed publisher
    ..These SNPs explain a considerable proportion of genetic variance, however, the majority of genetic variance has yet to be explained. ..
  9. Qian J, Chen W, Lettau M, Podda G, Zörnig M, Kabelitz D, et al. Regulation of FasL expression: a SH3 domain containing protein family involved in the lysosomal association of FasL. Cell Signal. 2006;18:1327-37 pubmed
  10. Begonja A, Pluthero F, Suphamungmee W, Giannini S, Christensen H, Leung R, et al. FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets. Blood. 2015;126:80-8 pubmed publisher
    ..The F-BAR protein PACSIN2 is one of the most abundant BAR/F-BAR proteins in platelets and the only one reported to interact with the ..
  11. Semmler J, Kormann J, Srinivasan S, Köster A, Salzer D, Reppel M, et al. Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart. Pharmacol Res. 2018;128:200-210 pubmed publisher
    ..These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases. ..
  12. Giridharan S, Cai B, Vitale N, Naslavsky N, Caplan S. Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. Mol Biol Cell. 2013;24:1776-90, S1-15 pubmed publisher
    ..We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE...
  13. Sumoy L, Pluvinet R, Andreu N, Estivill X, Escarceller M. PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of the pacsin-syndapin-FAP52 gene family. Gene. 2001;262:199-205 pubmed
    ..murine Pacsin genes have been reported to date: Pacsin 1 (equivalent to rat Syndapin I), and Pacsin 2 (like rat Syndapin II and chicken focal adhesion protein FAP52)...
  14. de Kreuk B, Anthony E, Geerts D, Hordijk P. The F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J Biol Chem. 2012;287:43438-53 pubmed publisher
    ..In this study, we identify a novel role for the F-BAR protein PACSIN2 in the regulation of EGF receptor signaling...
  15. Ghadimi M, Sanzenbacher R, Thiede B, Wenzel J, Jing Q, Plomann M, et al. Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178). FEBS Lett. 2002;519:50-8 pubmed
    ..peptide mass fingerprints correspond to Grb2, actin, beta-tubulin, formin binding protein 17 (FBP17) and PACSIN2. Grb2 had been identified as a putative mediator of T-cell receptor-to-CD95L signaling before...
  16. Ritter B, Modregger J, Paulsson M, Plomann M. PACSIN 2, a novel member of the PACSIN family of cytoplasmic adapter proteins. FEBS Lett. 1999;454:356-62 pubmed
  17. Eeles R, Kote Jarai Z, Al Olama A, Giles G, Guy M, Severi G, et al. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet. 2009;41:1116-21 pubmed publisher
    ..In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)). ..
  18. Smid A, Karas Kuzelicki N, Jazbec J, Mlinaric Rascan I. PACSIN2 polymorphism is associated with thiopurine-induced hematological toxicity in children with acute lymphoblastic leukaemia undergoing maintenance therapy. Sci Rep. 2016;6:30244 pubmed publisher
    ..the individual and combined effects of genetic variants of folate pathway enzymes, as well as of polymorphisms in PACSIN2 and ITPA, on drug-induced toxicities by applying a multi-analytical approach including logistic regression (LR), ..
  19. Chandrasekaran R, Kenworthy A, Lacy D. Clostridium difficile Toxin A Undergoes Clathrin-Independent, PACSIN2-Dependent Endocytosis. PLoS Pathog. 2016;12:e1006070 pubmed publisher
    ..Confocal microscopy using fluorescently labeled TcdA shows significant colocalization of the toxin with PACSIN2-positive structures in cells during entry...
  20. Grimm Günter E, Milbrandt M, Merkl B, Paulsson M, Plomann M. PACSIN proteins bind tubulin and promote microtubule assembly. Exp Cell Res. 2008;314:1991-2003 pubmed publisher
    ..These findings suggest a novel function for PACSIN proteins in dynamic microtubuli nucleation. ..
  21. Bai X, Zheng X. Tip-to-tip interaction in the crystal packing of PACSIN 2 is important in regulating tubulation activity. Protein Cell. 2013;4:695-701 pubmed publisher
  22. Kessels M, Dong J, Leibig W, Westermann P, Qualmann B. Complexes of syndapin II with dynamin II promote vesicle formation at the trans-Golgi network. J Cell Sci. 2006;119:1504-16 pubmed
    ..We demonstrate that the ubiquitously expressed syndapin II isoform interacts with the proline-rich domain (PRD) of dynamin II through its Src-homology 3 (SH3) domain...
  23. Senju Y, Rosenbaum E, Shah C, Hamada Nakahara S, Itoh Y, Yamamoto K, et al. Phosphorylation of PACSIN2 by protein kinase C triggers the removal of caveolae from the plasma membrane. J Cell Sci. 2015;128:2766-80 pubmed publisher
    b>PACSIN2, a membrane-sculpting BAR domain protein, localizes to caveolae. Here, we found that protein kinase C (PKC) phosphorylates PACSIN2 at serine 313, thereby decreasing its membrane binding and tubulation capacities...
  24. Meng H, Tian L, Zhou J, Li Z, Jiao X, Li W, et al. PACSIN 2 represses cellular migration through direct association with cyclin D1 but not its alternate splice form cyclin D1b. Cell Cycle. 2011;10:73-81 pubmed
    ..The cyclin D1-associated protein, PACSIN 2, regulates cell spreading and migration, which are dependent on cyclin D1 expression. ..
  25. Cuajungco M, Grimm C, Oshima K, D hoedt D, Nilius B, Mensenkamp A, et al. PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4. J Biol Chem. 2006;281:18753-62 pubmed
    ..Such a functional interaction could be important in cell types that show distribution of both proteins to the same subcellular regions such as renal tubule cells where the proteins are associated with the luminal plasma membrane. ..
  26. Zarnegar S, Durham B, Khattar P, Shukla N, Benayed R, Lacouture M, et al. Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis. Pediatr Blood Cancer. 2018;65: pubmed publisher
    ..Here, we report the discovery of a novel BRAF kinase fusion, PACSIN2-BRAF, in a child with multisystem LCH...
  27. Shimada A, Takano K, Shirouzu M, Hanawa Suetsugu K, Terada T, Toyooka K, et al. Mapping of the basic amino-acid residues responsible for tubulation and cellular protrusion by the EFC/F-BAR domain of pacsin2/Syndapin II. FEBS Lett. 2010;584:1111-8 pubmed publisher
    The extended Fes-CIP4 homology (EFC)/FCH-BAR (F-BAR) domain tubulates membranes. Overexpression of the pacsin2 EFC/F-BAR domain resulted in tubular localization inside cells and deformed liposomes into tubules in vitro...
  28. Yao G, Su X, Nguyen V, Roberts K, Li X, Takakura A, et al. Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex. Hum Mol Genet. 2014;23:2769-79 pubmed publisher
    ..Disruption of this complex contributes to cyst formation in PKD. ..