Uses
This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor. Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynanim, synaptojanin, endophilin, and clathrin. Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process. Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in ten transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described. (provided by RefSeq)
Biological Activity
The N-terminal BAR domain of Bridging integrator-1 (BIN1) is responsible for the regulation of membrane curvature sensing and generation (MC-S&G). This function of BIN1, in turn is regulated and auto-inhibited by the PI binding motif and the SH3 domain, which recruit downstream proteins such as dynamin-2. It interacts with Myc oncoproteins and acts as a tumor suppressor gene, and therefore, its expression is reduced in cancer cells. BIN1 also mediates endocytosis in brain by binding to AP2 and clathrin, which are endocytic proteins. BIN1 mediates endocytosis, cell migration, and endosomal sorting through membrane remodeling. This is achieved via its N-BAR domain, which mediates the formation of plasma membrane invaginations (T-tubules) in muscles. Centronuclear myopathy (CNM) has been linked to 3 mutations in the N-BAR gene, namely, K35N, D151N and R154Q. It has also been linked to late-onset Alzheimerμs disease and heart failure.
