Homer1

Homer1 is a gene that encodes a scaffold protein involved in organizing protein complexes at excitatory synapses in the brain. It belongs to the Homer family of proteins, which are characterized by a conserved N-terminal Homer homology domain (CHD) and a C-terminal coiled-coil domain. There are typically three mammalian isoforms: Homer1a, Homer1b, and Homer1c, arising from alternative splicing of the Homer1 gene.

Homer1 proteins act as molecular adaptors, linking transmembrane receptors like metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors to intracellular signaling molecules such as IP3 receptors and actin-binding proteins. This scaffolding function is crucial for maintaining synaptic structure and function, and for regulating synaptic plasticity, the ability of synapses to strengthen or weaken over time.

The Homer1a isoform is a short, non-transmembrane protein that is rapidly induced by neuronal activity and is thought to act as an inhibitor or antagonist of the longer Homer1b and Homer1c isoforms. This dynamic regulation by Homer1a plays a role in modulating synaptic responses and is implicated in learning and memory processes. Dysregulation of Homer1 function has been associated with various neurological and psychiatric disorders, including addiction, depression, and schizophrenia, highlighting its importance in brain health.