title: 14-3-3γ-Mediated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo.
abstract: The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here, we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin and other desmosomal proteins to the cell border in HCT116 cells and cells of the mouse testis. 14-3-3γ binds to plakoglobin in a PKCμ-dependent fashion, resulting in microtubule-dependent transport of plakoglobin to cell borders. Transport of plakoglobin to the border is dependent on the KIF5B-KLC1 complex. Knockdown of KIF5B in HCT116 cells, or in the mouse testis, results in a phenotype similar to that observed upon 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro, and in the mouse testis in vivo, leading to defects in testis organization and spermatogenesis.
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Lalit
authors.initials: L
authors.lastname: Sehgal
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Anandi
authors.initials: A
authors.lastname: Rajan
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Nileema
authors.initials: N
authors.lastname: Khapare
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Mugdha
authors.initials: M
authors.lastname: Sawant
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Sonali S
authors.initials: SS
authors.lastname: Vishal
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Khyati
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Srikant
authors.initials: S
authors.lastname: Ambatipudi
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Noelle
authors.initials: N
authors.lastname: Antao
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Hunain
authors.initials: H
authors.lastname: Alam
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Mansa
authors.initials: M
authors.lastname: Gurjar
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mathur
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Borde
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Amol S
authors.initials: AS
authors.lastname: Hosing
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Milind M
authors.initials: MM
authors.lastname: Vaidya
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Thorat
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors.forename: Ullas
authors.initials: U
authors.lastname: Kolthur-Seetharam
authors.affiliation: KS215, ACTREC, Tata Memorial Centre Kharghar Node, Navi Mumbai 410210, India sdalal@actrec.gov.in.
authors.forename: Sorab N
authors.initials: SN
authors.lastname: Dalal
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002448:Cell Adhesion / Q000502:physiology; D003896:Desmosomes / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D066298:In Vitro Techniques; D007248:Infertility, Male / Q000378:metabolism; D016547:Kinesins; D008297:Male; D051379:Mice; D051185:gamma Catenin / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C000715688:KLC1 protein, human; C000715695:Kns2 protein, mouse; D051185:gamma Catenin; D016547:Kinesins
keywords: 14-3-3γ; Desmosome; KIF5B; Plakoglobin; Spermatogenesis