LRRC7 explained

Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene.^[1]

Structure

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.^[2]

Interactions

LRRC7 has been shown to interact with CDH2.^[3]

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/]

Further reading

• Apperson ML, Moon IS, Kennedy MB . Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. . J. Neurosci. . 16 . 21 . 6839–52 . 1996 . 8824323 . 6579252 . 10.1523/JNEUROSCI.16-21-06839.1996.
• Nagase T, Kikuno R, Ishikawa KI, etal . Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. . DNA Res. . 7 . 1 . 65–73 . 2000 . 10718198 . 10.1093/dnares/7.1.65 . free .
• Walikonis RS, Oguni A, Khorosheva EM, etal . Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin. . J. Neurosci. . 21 . 2 . 423–33 . 2001 . 11160423 . 6763799 . 10.1523/JNEUROSCI.21-02-00423.2001.
• Izawa I, Nishizawa M, Ohtakara K, Inagaki M . Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses. . J. Biol. Chem. . 277 . 7 . 5345–50 . 2002 . 11729199 . 10.1074/jbc.M110052200 . free .
• Ohtakara K, Nishizawa M, Izawa I, etal . Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1. . Genes Cells . 7 . 11 . 1149–60 . 2003 . 12390249 . 10.1046/j.1365-2443.2002.00589.x . free .
• Wang L, Xu J, Wu Q, etal . Cloning and characterization of a novel splice variant of the brain-specific protein densin-180. . Int. J. Mol. Med. . 11 . 2 . 257–60 . 2003 . 12525888 . 10.3892/ijmm.11.2.257.
• Ahola H, Heikkilä E, Aström E, etal . A novel protein, densin, expressed by glomerular podocytes. . J. Am. Soc. Nephrol. . 14 . 7 . 1731–7 . 2003 . 12819232 . 10.1097/01.ASN.0000075553.33781.9F . free .
• Goodchild RE, Dauer WT . The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. . J. Cell Biol. . 168 . 6 . 855–62 . 2005 . 15767459 . 10.1083/jcb.200411026 . 2171781 .
• Robison AJ, Bass MA, Jiao Y, etal . Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. . J. Biol. Chem. . 280 . 42 . 35329–36 . 2005 . 16120608 . 10.1074/jbc.M502191200 . free .
• Gregory SG, Barlow KF, McLay KE, etal . The DNA sequence and biological annotation of human chromosome 1. . Nature . 441 . 7091 . 315–21 . 2006 . 16710414 . 10.1038/nature04727 . 2006Natur.441..315G . free .
• Rinta-Valkama J, Aaltonen P, Lassila M, etal . Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes. . Diabetes Metab. Res. Rev. . 23 . 2 . 119–26 . 2007 . 16741999 . 10.1002/dmrr.655 . 30494486 .
• Lassila M, Juhila J, Heikkilä E, Holthöfer H . Densin is a novel cell membrane protein of Sertoli cells in the testis. . Mol. Reprod. Dev. . 74 . 5 . 641–5 . 2007 . 17039495 . 10.1002/mrd.20659 . 43409823 .
• Ewing RM, Chu P, Elisma F, etal . Large-scale mapping of human protein-protein interactions by mass spectrometry. . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 .
• Heikkilä E, Ristola M, Endlich K, etal . Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions. . Mol. Cell. Biochem. . 305 . 1–2 . 9–18 . 2007 . 17581699 . 10.1007/s11010-007-9522-6 . 31301047 .

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

Notes and References

1. Web site: Entrez Gene: LRRC7 leucine rich repeat containing 7.
2. Thalhammer A, Trinidad JC, Burlingame AL, Schoepfer R . Densin-180: revised membrane topology, domain structure and phosphorylation status . J. Neurochem. . 109 . 2 . 297–302 . April 2009 . 19187442 . 10.1111/j.1471-4159.2009.05951.x . 2846389 .
3. Izawa . Ichiro . Nishizawa Miwako . Ohtakara Kazuhiro . Inagaki Masaki . Feb 2002 . Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses . J. Biol. Chem. . 277 . 7 . 5345–50 . United States. 0021-9258. 11729199 . 10.1074/jbc.M110052200 . free .