title: Bin3 deletion causes cataracts and increased susceptibility to lymphoma during aging.
abstract: Bin3 encodes an evolutionarily conserved and ubiquitously expressed member of the BAR superfamily of curved membrane and GTPase-binding proteins, which includes the BAR, PCH/F-BAR, and I-BAR adapter proteins implicated in signal transduction and vesicular trafficking. In humans, Bin3 maps to chromosome 8p21.3, a region widely implicated in cancer suppression that is often deleted in non-Hodgkin's lymphomas and various epithelial tumors. Yeast studies have suggested roles for this gene in filamentous actin (F-actin) organization and cell division but its physiologic functions in mammals have not been investigated. Here we report that homozygous inactivation of Bin3 in the mouse causes cataracts and an increased susceptibility to lymphomas during aging. The cataract phenotype was marked by multiple morphologic defects in lens fibers, including the development of vacuoles in cortical fibers and a near total loss of F-actin in lens fiber cells but not epithelial cells. Through 1 year of age, no other phenotypes were apparent; however, by 18 months of age, Bin3(-/-) mice exhibited a significantly increased incidence of lymphoma. Bin3 loss did not affect normal cell proliferation, F-actin organization, or susceptibility to oncogenic transformation. In contrast, it increased the proliferation and invasive motility of cells transformed by SV40 large T antigen plus activated ras. Our findings establish functions for Bin3 in lens development and cancer suppression during aging. Further, they define Bin3 as a candidate for an unidentified tumor suppressor that exists at the human chromosome 8p21.3 locus.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
authors.forename: Arivudainambi
authors.initials: A
authors.lastname: Ramalingam
authors.forename: James B
authors.initials: JB
authors.lastname: Duhadaway
authors.forename: Erika
authors.initials: E
authors.lastname: Sutanto-Ward
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Joseph
authors.initials: J
authors.lastname: Dinchuk
authors.forename: Minzhou
authors.initials: M
authors.lastname: Huang
authors.forename: Preston S
authors.initials: PS
authors.lastname: Donover
authors.forename: Janette
authors.initials: J
authors.lastname: Boulden
authors.forename: Lois M
authors.initials: LM
authors.lastname: McNally
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Soler
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Muller
authors.forename: Melinda K
authors.initials: MK
authors.lastname: Duncan
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
mesh_terms: D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D019556:COS Cells; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D000199:Actins; D008840:Microfilament Proteins