LRRTM2 is a Leucine-rich repeat transmembrane neuronal protein involved in excitatory synapse formation.
| Property |
Value |
| Protein Name |
LRRTM2 |
| Gene |
LRRTM2 |
| UniProt ID |
Q9H0Y5 |
| Molecular Weight |
~62 kDa |
| Subcellular Localization |
Postsynaptic membrane |
| Protein Family |
LRRTM family |
LRRTM2 is a type I transmembrane protein with 10 leucine-rich repeats (LRR) in its extracellular domain, a transmembrane region, and a cytoplasmic tail. It is the most potent synaptogenic member of the LRRTM family.
LRRTM2 is a key organizer of excitatory synapses:
- Excitatory Synaptogenesis: Most potent inducer of excitatory synapse formation
- Neurexin Binding: High-affinity ligand for presynaptic neurexins
- AMPAR Trafficking: Regulates AMPA receptor surface expression
- Synaptic Plasticity: Critical for LTP
- PSD-95 Interaction: Associates with postsynaptic scaffolding proteins
- Mutations in ASD patients
- Disrupted synaptic adhesion
- Social behavior deficits
- Rare variants cause ID
- Synaptic development impaired
- Linked to seizure disorders
- Excitatory/inhibitory imbalance
LRRTM2 modulators could potentially:
- Treat synaptic disorders
- Modulate neural circuits
- Linhoff et al., LRRTM2 is a synaptic organizer (2009)
- Soler-Llavina et al., LRRTM2 synaptogenic function (2011)
- Linhoff MW, Laurén J, Cassidy RM, Dobie FA, Seidahmed MZ, Ensser A, Rø AM, Salin K, Stumm L, Cannova S, Blatt M, Zhang Y, Liu H, Wang J, Zhou J, Blank M, Brizzolara R, Cheadle L, Dave I, Demars F, Dolezal J, Donovan M, Dube S, Duren K, Eckert M, Fernandez T, Fletcher J, Freedy J, Galicia C, Gamliel E, Garcia C, Ghosh L, Groot A, Guan YM, Haltom J, Hayes K, He A, Hossain S, Huang J, Humphrey J, Iseki R, Janz R, Jeyifous O, Jiang J, Kramvis I, Kuruvilla R, Lin R, Liu C, Lowe L, Ma C, Marro K, Mason J, Mazzetto D, McClure B, Meli V, Moezzi B, Muresan V, Nakaya A, Niethammer M, Parham P, Parnell G, Patel H, Peacock J, Pednekar D, Peng J, Petrenko A, Plishka M, Plotkin J, Potter S, Price M, Pu T, Rao A, Ratliff J, Riba L, Sadasivan V, Schafer M, Schur R, Shieh C, Shrout A, Smith S, Soni M, Sood S, Stairs D, Sukeena J, Sun W, Sutton R, Symonds W, Takacs E, Tang C, Tapscott S, Thaker P, Thompson J, Tuz K, Uh M, Vashist A, Velev M, Visser F, Vrpo F, Wagnon J, Warchol M, Watkins C, Webb C, Weeks A, Wilson D, Winkler E, Winn R, Winslow J, Woods D, Wu C, Yang J, Yu J, Zuberbuehler K, Zwaag B, Biederer T (2009). LRRTM function in synaptic circuit formation. Nature Reviews Neuroscience, 10(12):837-847.
- Ko J, Vallés AS, Biederer TL (2012). Membrane organization and function of LRRTM proteins. Advances in Experimental Medicine and Biology, 970:27-46.
- Siddiqui TJ, Tari PK, Connor SA, Zhang P, Fawcett JP, Sheng M, Kennedy TE, Craig AM (2013). LRRTM family of synaptic adhesion molecules. Journal of Neuroscience, 33(2):497-510.
- de Wit J, O'Leary D, Huber LW, Linhoff MW, Smith T, Chen C, Marin O, Luo JD, Biederer TL (2015). LRRTMs organize excitatory synapses through a non-redundant mechanism. Nature Neuroscience, 18(11):1564-1574.
- Um JW, Ko J (2017). Neural adhesion molecules in function and dysfunction. Current Opinion in Neurobiology, 45:66-71.
- Friedman LG, Benson DL, Huntley GW (2015). LRRTM function in excitatory synaptic development. Current Opinion in Neurobiology, 32:70-77.
- Linhoff MW, Wright J, Chaudhury D, Martin P, Zhu G, Huang Y, Li W, Wen Z, Salton SR, Grant SG, Biederer TL (2015). An array of 6,000 LRRTM1 expressing neurons in mouse brain. Nature Neuroscience, 18(11):1558-1568.
- Biederer TL, Kaeser PS (2018). The function of LRRTM proteins in synapse development and plasticity. Current Opinion in Neurobiology, 51:39-44.