The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300

TY - JOUR

T1 - The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300

AU - Zhang, Q P

AU - Ragnauth, C

AU - Greener, M J

AU - Shanahan, C M

AU - Roberts, R G

PY - 2002

Y1 - 2002

N2 - Nesprin-1 and nesprin-2 (also known as Syne-1 and Syne-2,) are large (similar to 3300-residue) vertebrate proteins associated with emerin and lamin A at the nuclear envelope of muscle cells and other cell types. We show that the previously described nesprins are short isoforms of giant proteins comprising an actin-binding amino-terminus connected to a carboxy-terminal klarsicht-related transmembrane domain by a massive (similar to 6000-8000 amino acid) spectrin-like rod domain, making full-length nesprin-1, at one megadalton, the largest non-titin protein hitherto described in humans. We find that MSP-300, a 7000-residue Drosophila melanogaster protein whose disruption results in defects of muscle development, corresponds to the N-terminal two-thirds of the Drosophila nesprin ortholog.:A nesprin-like protein is also encoded by the nematode genome. Moreover, we demonstrate that the larger isoforms of nesprin-1, like MSP-300, are localized to the sarcomeric Z-line of both skeletal and cardiac muscle. The recognition that a characteristic muscle-specific mutant phenotype in the fly results from a disruption of its nesprin ortholog reinforces the candidacy of the human proteins for involvement in genetic diseases of skeletal and cardiac muscle.

AB - Nesprin-1 and nesprin-2 (also known as Syne-1 and Syne-2,) are large (similar to 3300-residue) vertebrate proteins associated with emerin and lamin A at the nuclear envelope of muscle cells and other cell types. We show that the previously described nesprins are short isoforms of giant proteins comprising an actin-binding amino-terminus connected to a carboxy-terminal klarsicht-related transmembrane domain by a massive (similar to 6000-8000 amino acid) spectrin-like rod domain, making full-length nesprin-1, at one megadalton, the largest non-titin protein hitherto described in humans. We find that MSP-300, a 7000-residue Drosophila melanogaster protein whose disruption results in defects of muscle development, corresponds to the N-terminal two-thirds of the Drosophila nesprin ortholog.:A nesprin-like protein is also encoded by the nematode genome. Moreover, we demonstrate that the larger isoforms of nesprin-1, like MSP-300, are localized to the sarcomeric Z-line of both skeletal and cardiac muscle. The recognition that a characteristic muscle-specific mutant phenotype in the fly results from a disruption of its nesprin ortholog reinforces the candidacy of the human proteins for involvement in genetic diseases of skeletal and cardiac muscle.

UR - http://www.scopus.com/inward/record.url?scp=0036429266&partnerID=8YFLogxK

U2 - 10.1016/S0888-7543(02)96859-X

DO - 10.1016/S0888-7543(02)96859-X

M3 - Article

VL - 80

SP - 473

EP - 481

JO - Genomics

JF - Genomics

IS - 5

ER -