Profilin1 biology and its mutation, actin(g) in disease.
Profilins were discovered in the 1970s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to amyotrophic lateral sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we will discuss the implications of mutant profilin1 in various diseases with an emphasis on its contribution to the pathogenesis of ALS.
Department of Pharmacology and Toxicology, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA.
Duah
D
Alkam
Department of Pharmacology and Toxicology, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA.
Ezra Z
EZ
Feldman
Department of Pharmacology and Toxicology, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA.
Awantika
A
Singh
Department of Pharmacology and Toxicology, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. mkiaei@uams.edu.|Department of Neurology, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. mkiaei@uams.edu.|Department of Geriatrics, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. mkiaei@uams.edu.|The Center for Translational Neuroscience, The University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. mkiaei@uams.edu.
Mahmoud
M
Kiaei
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology; D004194:Disease / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009473:Neuronal Plasticity; D051304:Profilins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D000199:Actins; D051304:Profilins
Actin-binding domain; Axonal dynamics; Motor neuron disease; Neurodegeneration; PFN1 aggregation; PFN1 instability; PFN1G118V; PLP domain; Polymerization
J Neurosci. 2014 Mar 26;34(13):4443-4
24671990
J Med Genet. 2006 May;43(5):461-4
16371500
Curr Biol. 2003 Apr 1;13(7):534-45
12676083
Science. 2016 Jan 8;351(6269):173-6
26634439
Biol Chem. 2016 Sep 1;397(9):927-37
27101547
Neurobiol Aging. 2013 Sep;34(9):2235.e7-10
23635659
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):557-62
24899262
J Biol Chem. 1999 Dec 24;274(52):36963-72
10601251
Trends Cell Biol. 2003 Aug;13(8):435-46
12888296
Circ Res. 2007 Aug 17;101(4):357-67
17615372
Hum Mol Genet. 2011 Dec 15;20(24):4865-78
21920940
EMBO J. 2007 Jun 20;26(12):2991-3002
17541406
ACS Chem Biol. 2015 Nov 20;10 (11):2553-63
26226631
Bioessays. 2009 Nov;31(11):1150-60
19795407
Neurobiol Aging. 2013 Jul;34(7):1922.e1-5
23428184
Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):7984-9
26056300
Plant Sci. 2012 May;187:10-8
22404828
J Biol Chem. 2003 May 30;278(22):20268-77
12654920
Hum Pathol. 2015 May;46(5):673-80
25704627
Am J Physiol Heart Circ Physiol. 2010 Jun;298(6):H2112-20
20400688
Trends Cell Biol. 2004 Aug;14(8):461-9
15308213
Bioessays. 2008 Oct;30(10):994-1002
18798527
Sci Rep. 2015 Jul 31;5:12332
26227615
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3832-6
11274401
Science. 2006 Oct 6;314(5796):130-3
17023659
Development. 2014 Apr;141(7):1553-61
24598164
Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):3365-70
26951674
BMC Neurosci. 2015 Nov 16;16:77
26572741
J Mol Biol. 1977 Sep 25;115(3):465-83
563468
Amyotroph Lateral Scler Frontotemporal Degener. 2013 Sep;14(5-6):463-9
23634771
Nat Struct Biol. 1997 Nov;4(11):953-60
9360613
Neuroscience. 2012 Oct 25;223:355-64
22864186
Nat Cell Biol. 2012 Oct;14(10):985-7
23033049
Mol Cancer. 2014 Aug 07;13:187
25103363
Cell Adh Migr. 2012 Sep-Oct;6(5):442-9
23076048
Neurobiol Aging. 2013 May;34(5):1517.e9-10
23063648
PLoS One. 2012;7(1):e30068
22253883
J Neurosci. 2014 Jun 11;34(24):8083-97
24920614
J Cell Sci. 2006 Apr 15;119(Pt 8):1570-8
16569658
Neurobiol Aging. 2013 Apr;34(4):1311.e1-2
23062600
Cell Mol Life Sci. 2015 Nov;72(21):4193-203
26012696
Cardiovasc Diabetol. 2013 Oct 04;12 :141
24090212
Mol Biol Cell. 2004 Feb;15(2):896-907
14657240
J Biol Chem. 1994 Feb 11;269(6):4620-5
8308034
Nat Cell Biol. 2014 May;16(5):445-56
24747440
Glia. 2004 Jul;47(1):102-8
15139017
J Neurol. 2003 Apr;250(4):473-9
12700914
Am J Hum Genet. 1990 Mar;46(3):559-67
1968707
Nat Cell Biol. 2012 Oct;14(10):1046-56
23000962
Neurobiol Aging. 2013 Jun;34(6):1709.e1-2
23182804
Neuron. 2000 Jan;25(1):203-14
10707984
Adipocyte. 2014 Jan 1;3(1):69-74
24575374
Nature. 1993 Oct 28;365(6449):810-6
8413665
J Biol Chem. 2007 Dec 28;282(52):37632-9
17942408
Urology. 2014 Mar;83(3):675.e1-5
24581539
Hum Brain Mapp. 2013 Sep;34(9):2217-27
22461242
Ann Bot. 2014 Oct;114(6):1049-57
24769536
Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11
17084815
Trends Cell Biol. 2002 Mar;12(3):112-20
11859023
J Cell Sci. 2006 Oct 1;119(Pt 19):4127-37
16968742
Br J Cancer. 2007 Nov 19;97(10):1361-71
17940506
Clin Genet. 2003 Feb;63(2):83-101
12630951
Hum Mol Genet. 2016 Apr 1;25(7):1420-33
26908597
EMBO J. 2009 Apr 22;28(8):1157-69
19262563
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1060-6
24661873
J Cell Biol. 1999 Oct 4;147(1):151-62
10508862
J Cell Physiol. 2009 May;219(2):354-64
19115233
Cell Adh Migr. 2012 Jan-Feb;6(1):13-7
22647936
Plant Cell Rep. 2013 Jan;32(1):149-60
23052593
J Neurosci. 2011 Oct 5;31(40):14250-63
21976510
Cell. 2006 Jan 27;124(2):423-35
16439214
J Biol Chem. 2003 Feb 21;278(8):6291-300
12473661
Nature. 2012 Aug 23;488(7412):499-503
22801503
Neurobiol Aging. 2015 Mar;36(3):1602.e17-27
25499087
Proteomics. 2013 Jul;13(14):2100-12
23576398
Biomed Res Int. 2014;2014:947513
24987705
Neurobiol Aging. 2013 Jun;34(6):1708.e1-6
23141414
Protein Sci. 1995 Mar;4(3):450-9
7795529
Mol Cell Proteomics. 2012 Apr;11(4):M111.009449
22159600