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

Autor: Gesson, Kevin, Vidak, Sandra, Foisner, Roland
Rok vydání: 2014
Předmět:
congenital
hereditary
and neonatal diseases and abnormalities
BAF
barrier-to-autointegration factor
MDPSC
muscle-derived stem/progenitor cells
animal structures
ESC
embryonic stem cell
LEM
LAP2-Emerin-Man1
MSC
mesenchymal stem cell
Review
Nuclear envelopathies
FPLD
familial partial lipodystrophy
Retinoblastoma Protein
Muscular Dystrophies
Nuclear envelope
LAD
lamina-associated domain
Mice
Progeria
LAP
lamina-associated polypeptide
Animals
Humans
Nucleoplasmins
Dam
DNA adenine methyltransferase
DCM
dilated cardiomyopathy
Cell Proliferation
Adult stem cells
pRb
retinoblastoma protein
integumentary system
Laminopathies
INM
inner nuclear membrane
Membrane Proteins
Aging
Premature
Cell Differentiation
Cell Biology
Lamin Type A
Chromatin
Lamins
HGPS
Hutchinson–Gilford Progeria Syndrome
DNA-Binding Proteins
stomatognathic diseases
EDMD
Emery Dreifuss muscular dystrophy
Gene Expression Regulation
iPS
induced pluripotent stem cell
embryonic structures
ASC
(somatic) adult stem cell
NE
nuclear envelope
Self-renewal
LRD
lamin rich domain
Developmental Biology
Zdroj: Seminars in Cell & Developmental Biology
ISSN: 1084-9521
DOI: 10.1016/j.semcdb.2013.12.009
Popis: Highlights • A-type lamins localize to the lamina at the nuclear periphery and throughout the nucleoplasm. • A-type lamins in the nuclear interior bind to and depend on lamina-associated polypeptide 2α (LAP2α). • Lamin A/C–LAP2α complexes regulate tissue progenitor cell proliferation through retinoblastoma protein-linked pathways. • A-type lamins regulate chromatin organization and gene expression at the nuclear periphery and throughout the nucleoplasm. • Deregulation of nucleoplasmic A-type lamins and LAP2α contributes to abnormal phenotypes in laminopathies.
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 2α (LAP2α) in the regulation of A-type lamins in the nuclear interior. The lamin A/C–LAP2α 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 LAP2α 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 LAP2α 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.
Databáze: OpenAIRE
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