Wikipedia / BIN1
Wikipedia / BIN1
Myc box‑dependent‑interacting protein 1 (BIN1), also known as bridging integrator 1 and amphiphysin‑2, is a protein that in humans is encoded by the BIN1 gene.
Function
This gene encodes multiple isoforms of a membrane‑associated adaptor protein that can localize to the cytoplasm and, in some contexts, the nucleus. One isoform was originally identified as a MYC-interacting protein with characteristics of a tumor suppressor. BIN1 plays important roles in membrane curvature, endocytosis, and organization of specialized membrane structures such as transverse (T)‑tubules in striated muscle.
Nervous system
Isoforms expressed in the central nervous system participate in synaptic vesicle endocytosis and membrane trafficking through interactions with dynamin, endophilin, synaptojanin, and clathrin. Genetic variation at the BIN1 locus has been associated with risk of late‑onset Alzheimer's disease, and neuronal BIN1 isoforms interact with the microtubule‑associated protein tau.
Muscle and cellular functions
Muscle-specific and ubiquitously expressed isoforms are essential for the formation and maintenance of T-tubules and excitation–contraction coupling in skeletal and cardiac muscle. Certain nuclear-localized isoforms have been reported to modulate cell cycle progression and to induce an apoptotic or growth‑suppressive response independent of caspase activation in tumor cells.
Development and splicing
Studies in mice suggest that this gene plays an important role in cardiac muscle development and postnatal maturation of T-tubules. Alternative splicing of BIN1 generates numerous transcript variants encoding distinct isoforms with tissue‑specific expression patterns, and aberrant splice variants that attenuate BIN1 tumor-suppressor activity have been identified in several tumor cell lines and cancers.
Clinical significance
In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear myopathy causing muscle weakness and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects. An association has also been found between BIN1 mutations and Alzheimer's disease. Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish, and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.