LRRTM1 is a Leucine-rich repeat transmembrane neuronal protein involved in synaptic development and function.
| Property |
Value |
| Protein Name |
LRRTM1 |
| Gene |
LRRTM1 |
| UniProt ID |
Q9UHV9 |
| Molecular Weight |
~60 kDa |
| Subcellular Localization |
Postsynaptic membrane, cell surface |
| Protein Family |
LRRTM family |
LRRTM1 is a type I transmembrane protein with an N-terminal signal peptide, followed by 10 leucine-rich repeat (LRR) motifs, a transmembrane domain, and a short cytoplasmic tail. The LRR domain mediates protein-protein interactions with presynaptic partners including neurexins.
LRRTM1 is a potent synaptogenic molecule that organizes excitatory synapses:
- Synapse Formation: Induces both pre- and postsynaptic differentiation
- Neurexin Binding: Binds to presynaptic neurexins to trans-synaptically organize the synapse
- AMPAR Regulation: Regulates AMPA receptor trafficking and function
- Synaptic Plasticity: Involved in long-term potentiation and learning
- Postsynaptic Density: Localizes to PSD-95-containing postsynaptic densities
- Circuit Assembly: Critical for formation of neural circuits during development
- Altered expression in AD brains
- Synaptic dysfunction is early feature
- May modulate amyloid toxicity
- Genetic variants associated with PD risk
- Synaptic loss in PD models
- LRRTM1 mutations linked to ASD
- Social behavior deficits
LRRTM1 represents a potential therapeutic target for:
- Synaptic repair in neurodegeneration
- Modulating glutamatergic signaling
- Circuit repair strategies
- Linhoff et al., LRRTM1 is a synaptic organizer (2009)
- de Wit et al., LRRTM-neurexin interaction (2010)
- 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.