Lamina-associated polypeptide 2 alpha binds intranuclear A-type lamins

The nucleoskeletal protein lamina-associated polypeptide 2 alpha (LAP2 alph a) contains a large, unique C terminus and differs significantly from its a lternatively spliced, mostly membrane-integrated isoforms, such as LAP2 bet a, Unlike lamin B-binding LAP2 beta, LAP2 alpha was found by confocal immun ofluorescence microscopy to colocalize preferentially with 12-type lamins i n the newly formed nuclei assembled after mitosis. While only a subfraction of lamins A and C (lamin A/C) was associated with the predominantly nuclea r LAP2 alpha in telophase, the majority of lamin A/C colocalized with LAP2 alpha in G(1)-phase nuclei. Furthermore, selective disruption of A-type lam in structures by overexpression of lamin mutants in HeLa cells caused a red istribution of LAP2 alpha. Coimmunoprecipitation experiments revealed that a fraction of lamin A/C formed a stable, SDS-resistant complex with LAP2 al pha in interphase cells and in postmetaphase cell extracts. Blot overlay bi nding studies revealed a direct binding of LAP2 alpha to exclusively A-type lamins and located the interaction domains to the C-terminal 78 amino acid s of LAP2 alpha and to residues 319-566 in lamin A/C, which include the C t erminus of the rod and the entire tail common to lamin A/C. These findings suggest that LAP2 alpha and A-type lamins cooperate in the organization of internal nuclear structures.