Proteins that bind A-type lamins: integrating isolated clues.
What do such diverse molecules as DNA, actin, retinoblastoma protein and protein kinase Calpha all have in common? They and additional partners bind 'A-type' lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of tissue-specific diseases, termed 'laminopathies', including Emery-Dreifuss muscular dystrophy and the devastating Hutchinson-Gilford progeria syndrome, which mimics premature aging. Considered individually and collectively, partners for A-type lamins form four loose groups: architectural partners, chromatin partners, gene-regulatory partners and signaling partners. We describe 16 partners in detail, summarize their binding sites in A-type lamins, and sketch portraits of ternary complexes and functional pathways that might depend on lamins in vivo. On the basis of our limited current knowledge, we propose lamin-associated complexes with multiple components relevant to nuclear structure (e.g. emerin, nesprin 1alpha, actin) or signaling and gene regulation (e.g. LAP2alpha, retinoblastoma, E2F-DP heterodimers, genes) as 'food for thought'. Testing these ideas will deepen our understanding of nuclear function and human disease.
Zastrow
Michael S
MS
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Vlcek
Sylvia
S
Wilson
Katherine L
KL
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction
D002352:Carrier Proteins; D002843:Chromatin; D034904:Lamin Type A; D046911:Macromolecular Substances; D009687:Nuclear Proteins