Sunday 13 July 2003
Actin is the major component of the thin filaments of muscle cells and of the cytoskeletal system of nonmuscle cells. The amino acid sequences of muscle and cytoskeletal actin isoforms are very similar and well conserved in evolution.
Microfilaments, which are involved in cell motility, organelle transport, cytokinesis, and muscle contraction, are linear polymers of actin.
In mammalian nonmuscle cells, 2 classes of actin are recognized on isoelectric focusing gels: beta and gamma. These 2 isoforms differ by 4 amino acid substitutions at the conserved NH2-end of the molecule. They are coexpressed in nonmuscle cells.
The cadherin-catenin system
The formation of cadherin-mediated cell-cell junctions is accompanied by a profound remodeling of the actin cytoskeleton. The Arp2/3 complex and its activator cortactin drive the assembly of branching actin-filament arrays, and formin-1 promotes the nucleation of non-branching actin filaments.
Recruitment of these actin nucleators to nascent adhesions, formation of the links between them and the cytoplasmic cadherin domain, and triggering of their actin-polymerizing functions are vital steps in the development of cell-cell junctions.
Pathology of actins
|ACTC| idiopathic dilated cardiomyopathy |MIM.115200|
|ACTC| autosomal dominant hypertrophic cardiomyopathy |MIM.192600|
|ACT1A| nemaline myopathy |MIM.256030|
|ACT1A| congenital myopathy with excess of thin myofilaments |
|ACTG2| dominant Progressive Deafness (DFNA20/26)|
nucleation of actin filaments
assembly of actin filaments
disassembly of actin filaments
crosslinking of actin filaments
Pathology of actin polymerization
Lowe syndrome (mutations in the OCRL1 gene, which encodes a phosphatidylinositol 4,5 bisphosphate 5-phosphatase) (#12428211#)
smooth muscle actin
Small JV, Resch GP. The comings and goings of actin: coupling protrusion and retraction in cell motility. Curr Opin Cell Biol. 2005 Oct;17(5):517-23. PMID: #16099152#
Kovar DR. Molecular details of formin-mediated actin assembly. Curr Opin Cell Biol. 2006 Feb;18(1):11-7. PMID: #16364624#
Gourlay CW, Ayscough KR. The actin cytoskeleton: a key regulator of apoptosis and ageing? Nat Rev Mol Cell Biol. 2005 Jul;6(7):583-9. PMID: #16072039#
Lambrechts A, Van Troys M, Ampe C. The actin cytoskeleton in normal and pathological cell motility. Int J Biochem Cell Biol. 2004 Oct;36(10):1890-909. PMID: #15203104#
Chaponnier C, Gabbiani G. Pathological situations characterized by altered actin isoform expression. J Pathol. 2004 Nov;204(4):386-95. PMID: #15495226#
Ehrenberg M, McGrath JL. Actin motility: staying on track takes a little more effort. Curr Biol. 2004 Nov 9;14(21):R931-2. PMID: #15530387#
Bershadsky A. Magic touch: how does cell-cell adhesion trigger actin assembly? Trends Cell Biol. 2004 Nov;14(11):589-93. PMID: #15519846#
Paavilainen VO, Bertling E, Falck S, Lappalainen P. Regulation of cytoskeletal dynamics by actin-monomer-binding proteins. Trends Cell Biol. 2004 Jul;14(7):386-94. PMID: #15246432#
Vartiainen MK, Machesky LM. The WASP-Arp2/3 pathway: genetic insights. Curr Opin Cell Biol. 2004 Apr;16(2):174-81. PMID: #15196561#
Kwiatkowski AV, Gertler FB, Loureiro JJ. Function and regulation of Ena/VASP proteins. Trends Cell Biol. 2003 Jul ;13(7):386-92. PMID : #12837609#
Bamburg JR, Wiggan OP. ADF/cofilin and actin dynamics in disease. Trends Cell Biol. 2002 Dec;12(12):598-605. PMID: #12495849#
Condeelis J. How is actin polymerization nucleated in vivo? Trends Cell Biol. 2001 Jul;11(7):288-93. PMID: #11413039#