ArticleThe Journal of biological chemistry2016
A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): HINTS FOR AN INTRACELLULAR FUNCTION AT THE SYNAPSE.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
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- Genotype-Phenotype Correlations and Their Implications for Personalized Genetic Counseling in 103 Patients WithHuman mutation · 2026Article
- Functional Characterization and Pathogenicity Classification of PRRT2 Splice Variants in PRRT2-Related Disorders.Annals of clinical and translational neurology · 2025Article
- Slowed epigenetic aging in Olympic champions compared to non-champions.GeroScience · 2025Article
- Evaluating the Performance ofCombinatorial chemistry & high throughput screening · 2025Article
- SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion.bioRxiv : the preprint server for biology · 2024Article
- Paroxysmal Kinesigenic Dyskinesia: Genetics and Pathophysiological Mechanisms.Neuroscience bulletin · 2024Review
- Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia.Therapeutic advances in neurological disorders · 2024Article
- Pain-causing stinging nettle toxins target TMEM233 to modulate NaNature communications · 2023Article
- A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.Molecular neurobiology · 2023Article
- Functional regulation of syntaxin-1: An underlying mechanism mediating exocytosis in neuroendocrine cells.Frontiers in endocrinology · 2023Review
- Clinical characteristics and genetics of ten Chinese children with PRRT2-associated neurological diseases.Frontiers in pediatrics · 2022Article
- PRRT2 modulates presynaptic CaCell reports · 2021Article
- Beyond the AMPA receptor: Diverse roles of SynDIG/PRRT brain-specific transmembrane proteins at excitatory synapses.Current opinion in pharmacology · 2021Review
- Novel PRRT2 gene variants identified in paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy in Chinese families.Experimental and therapeutic medicine · 2021Article
- An interaction between PRRT2 and NaCell death & disease · 2021Article
- Exploring the Hereditary Nature of Migraine.Neuropsychiatric disease and treatment · 2021Review
- Interaction and Subcellular Association of PRRT1/SynDIG4 With AMPA Receptors.Frontiers in synaptic neuroscience · 2021Article
- Presynaptic PRRT2 Deficiency Causes Cerebellar Dysfunction and Paroxysmal Kinesigenic Dyskinesia.Neuroscience · 2020Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proline-rich transmembrane protein 2 (PRRT2) has been identified as the single causative gene for a group of paroxysmal syndromes of infancy, including epilepsy, paroxysmal movement disorders, and migraine. On the basis of topology predictions, PRRT2 has been assigned to the recently characterized family of Dispanins, whose members share the two-transmembrane domain topology with a large N terminus and short C terminus oriented toward the outside of the cell. Because PRRT2 plays a role at the synapse, it is important to confirm the exact orientation of its N and C termini with respect to the plasma membrane to get clues regarding its possible function. Using a combination of different experimental approaches, including live immunolabeling, immunogold electron microscopy, surface biotinylation and computational modeling, we demonstrate a novel topology for this protein. PRRT2 is a type II transmembrane protein in which only the second hydrophobic segment spans the plasma membrane, whereas the first one is associated with the internal surface of the membrane and forms a helix-loop-helix structure without crossing it. Most importantly, the large proline-rich N-terminal domain is not exposed to the extracellular space but is localized intracellularly, and only the short C terminus is extracellular (N cyt/C exo topology). Accordingly, we show that PRRT2 interacts with the Src homology 3 domain-bearing protein Intersectin 1, an intracellular protein involved in synaptic vesicle cycling. These findings will contribute to the clarification of the role of PRRT2 at the synapse and the understanding of pathogenic mechanisms on the basis of PRRT2-related neurological disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.