| Property | Value | [@friedman2015] |----------|-------| [@linhoff2015] | Protein Name | LRRTM1 | [@biederer2018] | Gene | LRRTM1 | | UniProt ID | Q9UHV9 | | Molecular Weight | ~60 kDa | | Subcellular Localization | Postsynaptic membrane, cell surface | | Protein Family | LRRTM family |
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Structure
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.
Normal Function
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](/mechanisms/long-term-potentiation) and learning
Postsynaptic Density: Localizes to PSD-95-containing postsynaptic densities
Circuit Assembly: Critical for formation of neural circuits during development
Role in Disease
Alzheimer's Disease
...
Overview
LRRTM1 is a Leucine-rich repeat transmembrane neuronal protein involved in synaptic development and function.
title: LRRTM1 Protein [@siddiqui2013] --- [@wit2015]
| Property | Value | [@friedman2015] |----------|-------| [@linhoff2015] | Protein Name | LRRTM1 | [@biederer2018] | Gene | LRRTM1 | | UniProt ID | Q9UHV9 | | Molecular Weight | ~60 kDa | | Subcellular Localization | Postsynaptic membrane, cell surface | | Protein Family | LRRTM family |
</div>
Structure
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.
Normal Function
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](/mechanisms/long-term-potentiation) and learning
Postsynaptic Density: Localizes to PSD-95-containing postsynaptic densities
Circuit Assembly: Critical for formation of neural circuits during development
Role in Disease
Alzheimer's Disease
Altered expression in AD brains
Synaptic dysfunction is early feature
May modulate amyloid toxicity
Parkinson's Disease
Genetic variants associated with PD risk
Synaptic loss in PD models
Autism Spectrum Disorder
LRRTM1 mutations linked to ASD
Social behavior deficits
Therapeutic Targeting
LRRTM1 represents a potential therapeutic target for:
Synaptic repair in neurodegeneration
Modulating glutamatergic signaling
Circuit repair strategies
Key Publications
[Linhoff et al., LRRTM1 is a synaptic organizer (2009)](https://doi.org/10.1016/j.neuron.2009.09.019)
[de Wit et al., LRRTM-neurexin interaction (2010)](https://doi.org/10.1016/j.neuron.2010.05.013)
[Unknown, 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 (2009)](https://pubmed.ncbi.nlm.nih.gov/19892942/)
[Unknown, Ko J, Vallés AS, Biederer TL (2012). Membrane organization and function of LRRTM proteins. Advances in Experimental Medicine and Biology, 970:27-46 (2012)](https://pubmed.ncbi.nlm.nih.gov/22639439/)
[Unknown, 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 (2013)](https://pubmed.ncbi.nlm.nih.gov/23303926/)
[Unknown, 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 (2015)](https://pubmed.ncbi.nlm.nih.gov/26322927/)
[Unknown, Um JW, Ko J (2017). Neural adhesion molecules in function and dysfunction. Current Opinion in Neurobiology, 45:66-71 (2017)](https://pubmed.ncbi.nlm.nih.gov/28415013/)
[Unknown, Friedman LG, Benson DL, Huntley GW (2015). LRRTM function in excitatory synaptic development. Current Opinion in Neurobiology, 32:70-77 (2015)](https://pubmed.ncbi.nlm.nih.gov/25612908/)
[Unknown, 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 (2015)](https://pubmed.ncbi.nlm.nih.gov/26322928/)
[Unknown, Biederer TL, Kaeser PS (2018). The function of LRRTM proteins in synapse development and plasticity. Current Opinion in Neurobiology, 51:39-44 (2018)](https://pubmed.ncbi.nlm.nih.gov/29454975/)