title: PINCH in the cellular stress response to tau-hyperphosphorylation.
abstract: Particularly interesting new cysteine- histidine- rich protein (PINCH) is an adaptor protein that our data have shown is required for neurite extension under stressful conditions. Our previous studies also report that PINCH is recalled by neurons showing decreased levels of synaptodendritic signaling proteins such as MAP2 or synaptophysin in the brains of human immunodeficiency virus (HIV) patients. The current study addressed potential role(s) for PINCH in neurodegenerative diseases. Mass spectrometry predicted the interaction of PINCH with Tau and with members of the heat shock response. Our in vitro data confirmed that PINCH binds to hyperphosphorylated (hp) Tau and to E3 ubiquitin ligase, carboxy-terminus of heat shock-70 interacting protein. Silencing PINCH prior to induction of hp-Tau resulted in more efficient clearance of accumulating hp-Tau, suggesting that PINCH may play a role in stabilizing hp-Tau. Accumulation of hp-Tau is implicated in more than 20 neuropathological diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD), and human immunodeficiency virus encephalitis (HIVE). Analyses of brain tissues from HIVE, AD and FTD patients showed that PINCH is increased and binds to hp-Tau. These studies address a new mechanism by which AD and HIV may intersect and identify PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau.
authors.affiliation: Temple University School of Medicine, Department of Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Ahmet Yunus
authors.initials: AY
authors.lastname: Ozdemir
authors.forename: Inna
authors.initials: I
authors.lastname: Rom
authors.forename: Jane
authors.initials: J
authors.lastname: Kovalevich
authors.forename: William
authors.initials: W
authors.lastname: Yen
authors.forename: Radhika
authors.initials: R
authors.lastname: Adiga
authors.forename: Rajnish S
authors.initials: RS
authors.lastname: Dave
authors.forename: Dianne
authors.initials: D
authors.lastname: Langford
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; C490232:Lims1 protein, mouse; C489788:MAP2 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases
references.citation: J Clin Invest. 2007 Mar;117(3):648-58
references.pmid: 17304350
references.citation: Biochim Biophys Acta. 2012 Mar;1823(3):648-55
references.pmid: 21856339
references.citation: PM R. 2011 Oct;3(10 Suppl 2):S460-7
references.pmid: 22035690
references.citation: J Biol Chem. 2005 Jul 29;280(30):27631-7
references.pmid: 15941716
references.citation: J Biol Chem. 2003 Jul 18;278(29):26970-5
references.pmid: 12714590
references.citation: Circulation. 2009 Aug 18;120(7):568-76
references.pmid: 19652092
references.citation: Am J Pathol. 2011 Apr;178(4):1646-61
references.pmid: 21435449
references.citation: BMC Neurosci. 2008 Dec 03;9 Suppl 2:S7
references.pmid: 19090995
references.citation: J Neurosci Res. 2008 Aug 15;86(11):2535-42
references.pmid: 18459134
references.citation: HPB (Oxford). 2010 Jun;12(5):352-8
references.pmid: 20590912
references.citation: Neurosci Lett. 1995 Jul 14;194(1-2):133-5
references.pmid: 7478197
references.citation: Neuroscience. 2009 Oct 6;163(2):561-70
references.pmid: 19555739
references.citation: J Biol Chem. 2002 Oct 11;277(41):38328-38
references.pmid: 12167643
references.citation: Mol Neurodegener. 2010 Jun 03;5:24
references.pmid: 20525284
references.citation: J Biol Chem. 2010 Jul 16;285(29):21978-87
references.pmid: 20466727
references.citation: J Biol Chem. 2008 Feb 1;283(5):2508-17
references.pmid: 18063582
references.citation: Acta Neuropathol. 2006 Jun;111(6):529-38
references.pmid: 16718349
references.citation: Biotechniques. 2004 Mar;36(3):402-4, 406
references.pmid: 15038154
references.citation: Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006437
references.pmid: 22229117
references.citation: Electrophoresis. 1999 Dec;20(18):3551-67
references.pmid: 10612281
references.citation: J Struct Biol. 2010 Apr;170(1):157-63
references.pmid: 19963065
references.citation: Mol Cell Biol. 2008 Jun;28(12):4018-25
references.pmid: 18411298
references.citation: J Cell Sci. 1999 Dec;112 ( Pt 24):4485-9
references.pmid: 10574698
references.citation: J Cell Biol. 2001 Apr 30;153(3):585-98
references.pmid: 11331308
references.citation: J Neuroimmune Pharmacol. 2011 Sep;6(3):330-40
references.pmid: 20689998
references.citation: Neuropharmacology. 2009 Oct-Nov;57(5-6):539-50
references.pmid: 19628001
references.citation: Hum Mol Genet. 2004 Apr 1;13(7):703-14
references.pmid: 14962978
references.citation: Biochemistry. 2012 Jan 31;51(4):888-98
references.pmid: 22236337
references.citation: Neuropathol Appl Neurobiol. 1994 Apr;20(2):103-10
references.pmid: 8072641
references.citation: Prog Neurobiol. 2011 Jan;93(1):99-110
references.pmid: 21056617
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9511-6
references.pmid: 17517623
references.citation: Toxicol Sci. 2011 Sep;123(1):193-205
references.pmid: 21715663
references.citation: Curr Alzheimer Res. 2010 Dec;7(8):677-84
references.pmid: 20678072
references.citation: Brain Res. 2010 Jul 23;1345:176-81
references.pmid: 20457142
references.citation: BMC Cancer. 2012 Feb 10;12:65
references.pmid: 22325464
references.citation: PLoS One. 2009 Nov 19;4(11):e7917
references.pmid: 19936237
references.citation: J Cell Sci. 2005 Jul 1;118(Pt 13):2913-21
references.pmid: 15976450
references.citation: Nat Struct Biol. 2003 Jul;10(7):558-64
references.pmid: 12794636
references.citation: Mol Biol Cell. 2010 Dec;21(23):4120-9
references.pmid: 20926685
references.citation: Neuron. 2007 Feb 1;53(3):337-51
references.pmid: 17270732
references.citation: J Neurochem. 2005 Sep;94(5):1254-63
references.pmid: 16111477
references.citation: Cancer. 2002 Sep 15;95(6):1387-95
references.pmid: 12216108
references.citation: J Neurosci. 2008 Nov 19;28(47):12163-75
references.pmid: 19020010