title: KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development.
abstract: Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and basal surfaces of the neuroblastic layer (NBL). This process is termed interkinetic nuclear migration (INM). Furthermore, newly formed photoreceptor cells migrate and form the outer nuclear layer (ONL). In the current study, we demonstrated that a KASH domain-containing protein, Syne-2/Nesprin-2, as well as SUN domain-containing proteins, SUN1 and SUN2, play critical roles during INM and photoreceptor cell migration in the mouse retina. A deletion mutation of Syne-2/Nesprin-2 or double mutations of Sun1 and Sun2 caused severe reduction of the thickness of the ONL, mislocalization of photoreceptor nuclei and profound electrophysiological dysfunction of the retina characterized by a reduction of a- and b-wave amplitudes. We also provide evidence that Syne-2/Nesprin-2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina. These key retinal developmental signaling results will advance our understanding of the mechanism of nuclear migration in the mammalian retina.
authors.affiliation: Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai 200433, China.
authors.forename: Juehua
authors.initials: J
authors.lastname: Yu
authors.forename: Kai
authors.initials: K
authors.lastname: Lei
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Craft
authors.forename: Gezhi
authors.initials: G
authors.lastname: Xu
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Rener
authors.initials: R
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012160:Retina / Q000737:chemistry / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C464932:SUN1 protein, mouse; C520338:Sun2 protein, mouse; C485901:Syne1 protein, mouse; D034501:Telomere-Binding Proteins