LRRC7

Description

The LRRC7 (leucine rich repeat containing 7) is a protein-coding gene located on chromosome 1.

LRRC7, also known as Densin-180 or LAP1, is a protein which in humans is encoded by the LRRC7 gene. Found to be densely associated to the postsynaptic density (PSD), it has been characterised as a 188 kDa (originally thought to be 180 kDa, hence nomenclature), 1495 residues long, brain-specific protein containing 16 leucine-rich repeats (LRRs) within the 500 N-terminal residues, and one Psd95/Discs large/Zona occludens (PDZ) domain within the 200 C-terminal residues. Originally postulated to have an apparent transmembrane domain, it has now been shown that the protein has numerous phosphorylation sites both N- and C-term of this domain, and that protein is therefore cytoplasmic; palmitoylation is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD. LRRC7 has been shown to interact with CDH2. The currently exposed interactions of Densin-180 portray the protein as a promiscuous player amongst key synaptic players, fitting with the original observation of the protein’s dense presence among core PSD proteins by Mary B. Kennedy's Laboratory. Identified interaction partners include: CaMKII-alpha, alpha-Actinin and NR2B (via CaMKII-alpha), Cav1.3 (L-type Ca2+) channels, MAGUIN-1, Shank, PSD-95 (via Shank and MAGUIN-1), beta-Catenin, delta-Catenins and NCadherin (via the Catenins). The nature and function of these interactions, detailed in tables 1-1 and 1-2, portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. It is also quite possible that Densin-180 dimerises or multimerises through interactions between its PDZ domain and its own terminal amino acid residues.

LRRC7 plays a crucial role in maintaining the structural integrity and proper functioning of synaptic spines, the small protrusions on neurons that receive signals from other nerve cells. It is essential for the correct positioning of DISC1 and GRM5, two key proteins involved in synaptic signaling, within the postsynaptic density (PSD), a complex structure at the synapse that anchors and regulates receptors and other signaling molecules. LRRC7 is also vital for both N-methyl D-aspartate receptor (NMDA)-dependent and metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), a type of synaptic plasticity that weakens the strength of connections between neurons.

LRRC7 is also known as DENSIN.

Associated Diseases

WES Whole Exome Sequencing