Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease

A-type lamins are components of the lamina network at the nuclear envelope, which mediates nuclear stiffness and anchors chromatin to the nuclear periphery. However, A-type lamins are also found in the nuclear interior. Here we review the roles of the chromatin-associated, nucleoplasmic LEM protein, lamina-associated polypeptide 2 alpha (LAP2 alpha) in the regulation of A-type lamins in the nuclear interior. The lamin A/C-LAP2 alpha complex may be involved in the regulation of the retinoblastoma protein-mediated pathway and other signaling pathways balancing proliferation and differentiation, and in the stabilization of higher-order chromatin organization throughout the nucleus. Loss of LAP2 alpha in mice leads to selective depletion of the nucleoplasmic A-type lamin pool, promotes the proliferative stem cell phenotype of tissue progenitor cells, and delays stem cell differentiation. These findings support the hypothesis that LAP2 alpha and nucleoplasmic lamins are regulators of adult stem cell function and tissue homeostasis. Finally, we discuss potential implications of this concept for defining the molecular disease mechanisms of lamin-linked diseases such as muscular dystrophy and premature aging syndromes. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.