复旦大学讲座特聘教授韩珉、徐人尔教授带领的研究小组在最近的PNAS上发表新的研究进展,SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice。
生物通报道:复旦大学讲座特聘教授韩珉、徐人尔教授带领的研究小组在最近的PNAS上发表新的研究进展,SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice。
SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice
Kai Leia,1, Xiaochang Zhanga,1, Xu Dinga, Xue Guoa, Muyun Chena, Binggen Zhua,2, Tian Xua,b, Yuan Zhuanga,c, Rener Xua,3 and Min Hana,d,3
-Author Affiliations
aInstitute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai 200433, China;
bHoward Hughes Medical Institute and Department of Genetics, Yale University School of Medicine, New Haven, CT 06520;
cDepartment of Immunology, Duke University Medical Center, Durham, NC 27710; and
dHoward Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309
【Abstract】
How the nuclei in mammalian skeletal muscle fibers properly position themselves relative to the cell body is an interesting and important cell biology question. In the syncytial skeletal muscle cells, more than 100 nuclei are evenly distributed at the periphery of each cell, with 3–8 nuclei anchored beneath the neuromuscular junction (NMJ). Our previous studies revealed that the KASH domain–containing Syne-1/Nesprin-1 protein plays an essential role in anchoring both synaptic and nonsynaptic myonuclei in mice. SUN domain–containing proteins (SUN proteins) have been shown to interact with KASH domain–containing proteins (KASH proteins) at the nuclear envelope (NE), but their roles in nuclear positioning in mice are unknown. Here we show that the synaptic nuclear anchorage is partially perturbed in Sun1, but not in Sun2, knockout mice. Disruption of 3 or all 4 Sun1/2 wild-type alleles revealed a gene dosage effect on synaptic nuclear anchorage. The organization of nonsynaptic nuclei is disrupted in Sun1/2 double-knockout (DKO) mice as well. We further show that the localization of Syne-1 to the NE of muscle cells is disrupted in Sun1/2 DKO mice. These results clearly indicate that SUN1 and SUN2 function critically in skeletal muscle cells for Syne-1 localization at the NE, which is essential for proper myonuclear positioning.