| Gene Symbol |
PTPRT |
| Full Name |
Protein Tyrosine Phosphatase Receptor Type T |
| Alias |
RPTPρ, RPTP-Sigma |
| Chromosomal Location |
20q12-q13.12 |
| NCBI Gene ID |
5792 |
| OMIM ID |
602706 |
| Ensembl ID |
ENSG00000196090 |
| UniProt ID |
Q9Y2P9 |
| Protein Family |
Receptor-type protein tyrosine phosphatase (RPTP) family |
| Associated Diseases |
[Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), Intellectual Disability, Colorectal Cancer |
PTPRT (Protein Tyrosine Phosphatase Receptor Type T), also known as RPTPρ or RPTP-Sigma, is a member of the receptor protein tyrosine phosphatase (RPTP) family. It is primarily expressed in the nervous system where it plays critical roles in regulating synaptic connectivity, neuronal migration, and axon guidance [moll1991]. PTPRT functions as a receptor-type phosphatase that dephosphorylates specific substrates involved in neuronal development and synaptic plasticity [besco2006].
PTPRT is unique among RPTPs due to its extended extracellular domain and brain-restricted expression pattern. The protein has emerged as an important regulator of neuronal connectivity and has been implicated in neurodevelopmental disorders and cancer.
PTPRT consists of:
- Extracellular domain: Contains multiple fibronectin type III repeats that mediate cell-cell interactions
- Transmembrane domain: Single pass membrane-spanning region
- Cytoplasmic domain: Contains two tandem tyrosine phosphatase domains (D1 and D2)
The D1 domain possesses catalytic activity and dephosphorylates substrate proteins, while the D2 domain may regulate substrate specificity or serve as a docking platform for signaling proteins.
In neurons, PTPRT performs several critical functions:
Synapse Formation and Function
PTPRT localizes to postsynaptic sites and regulates synaptic development [charette2020]:
- Controls the formation and maintenance of dendritic spines
- Regulates synaptic transmission through modulation of postsynaptic receptors
- Coordinates with presynaptic signaling molecules for proper synaptic alignment
Axon Guidance
During development, PTPRT directs axon pathfinding [engel2012]:
- Regulates growth cone dynamics
- Modulates cytoskeletal organization in response to guidance cues
- Coordinates with intracellular signaling pathways
Neuronal Migration
PTPRT influences neuronal positioning during cortical development [stoker2015]:
- Modulates adhesion dynamics during migration
- Interacts with cytoskeletal regulators
Dendrite Morphogenesis
The phosphatase regulates dendritic arborization and branching [wang2017]:
- Controls dendritic tree complexity
- Influences spine distribution along dendrites
PTPRT dephosphorylates several key substrates:
- Fyn kinase: Regulates Src family kinase activity at synapses
- PSD-95: Modulates synaptic scaffold organization [yang2013]
- NMDA receptor subunits: Alters receptor trafficking and function
- Actin cytoskeletal regulators: Controls spine morphology
PTPRT mutations are associated with ASD [farber2011]:
- Loss-of-function variants identified in ASD patients
- Haploinsufficiency may disrupt synaptic development
- Contributes to social behavior and communication deficits
- Synaptic formation deficits observed in PTPRT-deficient neurons [anderson2015]
PTPRT variants cause:
- Non-syndromic intellectual disability
- Developmental delay
- Speech and language impairments
As a tumor suppressor [beltran2013]:
- Frequently mutated in colorectal cancers [chen2018]
- Loss-of-function mutations promote cell proliferation
- Associated with poor prognosis in some cancers
Emerging evidence suggests roles in [park2023]:
- Synaptic dysfunction in Alzheimer's disease
- Axonal degeneration in Parkinson's disease
- Neuronal death in stroke models
- Proteolytic cleavage by ADAM10 and γ-secretase affects its function [lim2023]
- Primarily neural: Highest expression in brain and nervous system
- Lower expression: Detected in some epithelial tissues
- Developmentally regulated: Expression peaks during embryogenesis
- Cerebral cortex: Layer 2-6 pyramidal neurons
- Hippocampus: CA1-CA3 pyramidal cells and dentate gyrus granule cells
- Cerebellum: Purkinje cells and granule cells
- Brainstem: Various neuronal populations
- Spinal cord: Motor neurons and interneurons
- Postsynaptic density: Concentrated at excitatory synapses
- Growth cones: Present in developing axons
- Dendritic shafts: Along dendritic processes
- Neurons: Primary expression in excitatory glutamatergic neurons
- Astrocytes: Lower expression
- Oligodendrocytes: Limited expression
PTPRT is being explored as a therapeutic target:
- Inhibitors: Small molecule inhibitors for cancer treatment
- Activators: Compounds that enhance PTPRT function in neurodevelopmental disorders
- Blood-brain barrier considerations: Important for CNS applications
- Biomarkers: PTPRT expression as a marker for synaptic integrity
- Gene therapy: Restoring PTPRT function in neurodevelopmental disorders
- Combination therapies: Targeting PTPRT with other treatments
¶ Interactions and Pathways
- Ligands: PTPRT interacts with various cell adhesion molecules
- Substrates: Fyn, PSD-95, NMDA receptors
- Scaffolding proteins: Links to cytoskeletal organizers
- Src family kinases: Regulates Src signaling at synapses
- NMDA receptor signaling: Modulates glutamatergic transmission
- Integrin signaling: Coordinates adhesion and migration
- Moll et al., Identification of a new receptor-type tyrosine phosphatase (1991)
- Besco et al., PTPRT genomic organization and brain expression (2006)
- Sallee et al., Receptor protein tyrosine phosphatase function in development (2008)
- Beltran et al., PTPRT regulates colorectal cancer progression (2013)
- Zhang et al., Role of receptor tyrosine phosphatases in neural development (2019)
- Charette et al., PTPRT in synaptogenesis and neuronal connectivity (2020)
- Engel et al., Regulation of neuronal axon guidance (2012)
- Stoker & Dutta, Protein tyrosine phosphatases and neural development (2015)
- Farber et al., PTPRT mutations in autism spectrum disorder (2011)
- Liu et al., PTPRT expression and function in neuronal cells (2016)
- Wang et al., Receptor protein tyrosine phosphatases in brain development (2017)
- Chen et al., PTPRT as tumor suppressor in colorectal cancer (2018)
- Mori et al., PTPRT regulates dendritic spine morphology (2020)
- Kaufmann et al., Protein tyrosine phosphatases in synaptic plasticity (2022)
- Park et al., Role of receptor tyrosine phosphatases in neurodegeneration (2023)