title: A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit.
abstract: Fibulin-1 is a member of a growing family of proteins that includes eight members and is involved in cellular functions such as adhesion, migration and differentiation. Fibulin-1 has also been implicated in embryonic development of the heart and neural crest-derived structures. It is an integral part of the extracellular matrix (ECM) and has been shown to bind to a multitude of ECM proteins. However, fibulin-1 was first identified as a protein purified from placental extracts that binds to the cytoplasmic domain of integrin β1. Human fibulin-1 is alternatively spliced into four different isoforms namely A-D. These isoforms share a common N-terminus sequence that contains a secretion sequence but differ in their carboxy-terminal fibulin-1 module. In this report we identify a new splice variant of fibulin-1 that differs from all other fibulin-1 variants in the N-terminus sequence and has a similar carboxy-terminus sequence as fibulin-1D. This variant that we named fibulin-1D prime (fibulin-1D') lacks a secretion sequence and the anaphlatoxin region of fibulin-1 variants. The protein has an apparent molecular weight of 70.5kDa. Herein we show that fibulin-1D' binds to the intracellular domain of integrin β1 as well as to integrin α5β1. The protein was localized intracellularly in CHO cells transfected with a pEF4 plasmid containing full-length coding sequence of fibulin-1D'. We also localized the protein in human placenta. We propose that the fibulin-1D' variant might play a role in early embryo development as well as in modulating integrin β1 functions including adhesion and motility.
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, MSC 508, Charleston, SC 29412, USA. Electronic address: twalwo@musc.edu.
authors: Waleed O
authors: WO
authors: Twal
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, MSC 508, Charleston, SC 29412, USA. Electronic address: hammadsm@musc.edu.
authors: Samar M
authors: SM
authors: Hammad
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, MSC 508, Charleston, SC 29412, USA.
authors: Sharon L
authors: SL
authors: Guffy
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, MSC 508, Charleston, SC 29412, USA.
authors: William S
authors: WS
authors: Argraves
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D003412:Cricetulus; D005260:Female; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D020033:Protein Isoforms; C060820:fibulin
keywords: Fibulin-1D isoform; Integrin alpha 5 beta 1; Integrin β1; Intracellular localization; Placenta