TMEM132: an ancient architecture of cohesin and immunoglobulin domains define a new family of neural adhesion molecules

Abstract

SummaryThe molecular functions of TMEM132 genes remain poorly understood and under-investigated despite their mutations associated with non-syndromic hearing loss, panic disorder and cancer. Here we show the full domain architecture of human TMEM132 family proteins solved using in-depth sequence and structural analysis. We reveal them to be five previously unappreciated cell adhesion molecules whose domain architecture has an early holozoan origin prior to the emergence of choanoflagellates and metazoa. The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals. These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.Supplementary information Supplementary data are available at Bioinformatics online.

Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers

“…TMEM132D is a transmembrane protein also highly expressed in the brain [54]. Its function is still largely unknown but it has been suggested to serve as a cell surface marker for oligodendrocytes [55], and more recently, to possess celladhesion functions [56]. Although genetic variants in TMEM132D have been associated with primary psychiatric disorders [57], this is to our knowledge, the first report of TMEM132D in relation to FTD, but TMEM132D was one of the proteins for which the results from the first cohort could not be replicated with significance.…”

Genetic architecture underlying changes in carotenoid accumulation during the evolution of the blind Mexican cavefish, Astyanax mexicanus

“…We considered which of the genes in the VAT color QTL could influence carotenoid processing, based on known activities. Clip2 and tmem132 encode proteins that likely function in neurons and have roles in microtubule stability (Vandeweyer, Van Der Aa, Reyniers, & Kooy, 2012) and hair cell function, respectively (Sanchez‐Pulido & Ponting, 2018). Gtf2ird1 encodes a general transcription factor that is ubiquitously expressed.…”

Association of CSF Proteins With Tau and Amyloid β Levels in Asymptomatic 70-year-olds 

“…Neuronal pentraxin receptor (NPTXR), is another synaptic receptor protein that has been implicated in AD together with several of the proteins mentioned above (55,56). The transmembrane protein TMEM132D is highly expressed in the brain (57) and has been proposed to serve as an oligodendric cell surface marker (58) with cell-adhesion functions (59), although its main function still remains unknown. To our knowledge TMEM132D has not been studied in the context of AD but we previously observed altered levels in patients with frontotemporal dementia (32).…”