ArticleMolecular brain2021
The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex.
Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Neurodevelopmental alterations are key drivers of SPG56.Human molecular genetics · 2026Article
- TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression.Clinical and experimental medicine · 2026Article
- A human forebrain organoid model phenocopies dysregulated RNA and protein homeostasis in ALS/FTD-associated TDP-43 proteinopathies.bioRxiv : the preprint server for biology · 2025Article
- TMEM132D and VIPR2 Polymorphisms as Genetic Risk Loci for Retinal Detachment: A Genome-Wide Association Study and Polygenic Risk Score Analysis.Investigative ophthalmology & visual science · 2023Article
- Article
- TMEM132A regulates mouse hindgut morphogenesis and caudal development.Development (Cambridge, England) · 2023Article
- Differential expression of the Tmem132 family genes in the developing mouse nervous system.Gene expression patterns : GEP · 2022Article
- TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration.Development (Cambridge, England) · 2022Article
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.American journal of translational research · 2021Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
TMEM132D is a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Defining a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the sole TMEM132 ortholog in C. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations in C. elegans tmem-132 that disrupt interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects in tmem-132 mutants, whereas gain-of-function of TMEM132D in mammalian cells inhibits WRC, leading to decreased abundance of select WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.
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