Lamina-associated polypeptide 2 isoforms and related proteins in cell cycle-dependent nuclear structure dynamics

The lamina-associated polypeptide (LAP) 2 family comprises up to six altern atively spliced proteins in mammalian cells and three isoforms in Xenopus. LAP2 beta is a type II integral protein of the inner nuclear membrane, whic h binds to lamin B and the chromosomal protein BAF, and may link the nuclea r membrane to the underlying lamina and provide docking sites for chromatin . LAP2 alpha shares only the N-terminus with the other isoforms and contain s a unique C-terminus. It is a nonmembrane protein associated with the nucl eoskeleton and may help to organize higher order chromatin structure by int eracting with A-lamins and chromosomes. Recent studies using mutant protein s have just begun to unravel functions of LAP2 isoforms during postmitotic nuclear reassembly. LAP2 alpha associates with chromosomes via an alpha-spe cific domain at early stages of assembly, possibly providing a structural f ramework for chromosome reorganization. The subsequent interaction of both LAP2 alpha and LAP2 beta with the chromosomal BAF may stabilize chromatin s tructure and target membranes to the chromosomes. At later stages LAPS may regulate the assembly of lamins. LAP2 isoforms have been found to share a h omologous similar to 40 amino acid long region, the LEM domain, with nuclea r membrane proteins MAN1 and emerin, which has been implicated in Emery-Dre ifuss muscular dystrophy. (C) 2000 Academic Press.