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.
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Michael S
MS
Zastrow
Sylvia
S
Vlcek
Katherine L
KL
Wilson
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