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microfilaments

actins

Microfilaments are involved in cell motility, organelle transport, cytokinesis, and muscle contraction. Microfilaments are linear polymers of actin. The actin cytoskeleton plays critical roles in cell morphologic changes and motility.

Members

- alpha-actins: ACTA1, ACTA2
- beta-actins: ACTB
- cardiac-actins: ACTC
- gamma-actins: ACTG

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.

Regulation

Rho family small GTPases, such as Rho (MIM.165370), RAC (MIM.602048), and CDC42 (MIM.116952), organize the actin cytoskeleton. Other major players in actin-based motility are the 7 members of the ARP2/3 complex (MIM.604221).

The Wiskott-Aldrich syndrome protein (WASP) (MIM.301000), WASP-like (WASL) (MIM.605056), and WASF1 are among the downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton.

Pathology

- Wiskott-Aldrich syndrome and WASP mutations
- congenital myopathies

See also:

- actin-related proteins (ARPs)
- actin-binding proteins
- cytoskeleton

References

- 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

- Blessing CA, Ugrinova GT, Goodson HV. Actin and ARPs: action in the nucleus. Trends Cell Biol. 2004 Aug;14(8):435-42. PMID: 15308210

- Finkelstein LD, Schwartzberg PL. Tec kinases: shaping T-cell activation through actin. Trends Cell Biol. 2004 Aug;14(8):443-51. PMID: 15308211

- Behrendt B. FAP52 - a new partner for filamin in actin cytoskeleton organization. Trends Cell Biol. 2002 May;12(5):213. PMID: 12062164

- Rottner K, Lommel S, Wehland J, Stradal TE. Pathogen-induced actin filament rearrangement in infectious diseases. J Pathol. 2004 Nov;204(4):396-406. Review. PMID: 15495265

- Clarkson E, Costa CF, Machesky LM. Congenital myopathies: diseases of the actin cytoskeleton. J Pathol. 2004 Nov;204(4):407-17. PMID: 15495263