Fibulin-1
identical protein binding
A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit.
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.