LRRC7

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.{{cite journal |vauthors=Thalhammer A, Trinidad JC, Burlingame AL, Schoepfer R | title = Densin-180: revised membrane topology, domain structure and phosphorylation status | journal = J. Neurochem. | volume = 109 | issue = 2 | pages = 297–302 |date=April 2009 | pmid = 19187442 | doi = 10.1111/j.1471-4159.2009.05951.x | pmc = 2846389 }}

LRRC7 has been shown to interact with CDH2.{{cite journal |last=Izawa |first=Ichiro |author2=Nishizawa Miwako |author3=Ohtakara Kazuhiro |author4=Inagaki Masaki |date=Feb 2002 |title=Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses |journal=J. Biol. Chem. |volume=277 |issue=7 |pages=5345–50 |location = United States| issn = 0021-9258| pmid = 11729199 |doi = 10.1074/jbc.M110052200 |doi-access=free }}

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. [number of sources - referenced in - Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/]

It is also quite possible that Densin-180 dimerises or multimerises through interactions between its PDZ domain and its own terminal amino acid residues. [Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells

Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/]

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Add—a very detailed thesis with preliminary experiments and theories about the function of Densin-180 entitled Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells

http://discovery.ucl.ac.uk/1322972/

Category:LRR proteins