Abstract
Integral Membrane Protein 2 B (ITM2B) is a type II ubiquitous transmembrane protein which role remains unclear. ITM2B mutations have been associated with different disorders: mutations leading to longer mutant proteins have been reported in two distinct Alzheimer-like autosomal dominant disorders with early-onset progressive dementia and cerebellar ataxia. Both disorders share neurological features including severe cerebral amyloid angiopathy, non-neuritic plaques, and fibrillary tangles as in Alzheimer disease. Our group reported a missense mutation in ITM2B, in an unusual retinal dystrophy with no dementia. This finding suggests a specific role of ITM2B in the retina. As the identification of retinal-specific ITM2B partners could bring new insights into the cellular functions of ITM2B, we performed quantitative proteomics of ITM2B interactome of the human retina. Overall, 457 ITM2B partners were identified with 8 of them involved in visual transduction. In addition, bulk Gene Ontology analyses showed that many ITM2B partners are involved in several other biological functions, such as microtubule organization, protein translation and interestingly, mitochondrial homeostasis. These data represent the first report of the ITM2B interactome in the human retina and may serve as a valuable inventory of new potential ITM2B partners for future investigations of ITM2B physiological functions and dysfunctions.
Highlights
Integral Membrane Protein 2 B (ITM2B) (Integral membrane protein 2b called BRI2, MIM#603904) is a single pass type II ubiquitous protein which function is still unclear
Among 457 ITM2B potential interactors, we found tubulin beta-3 class III (TUBB3) and the neurofilament light polypeptide (NEFL) both highly expressed in retinal ganglion cells[20,21]
Among the significantly enriched proteins purified with the mouse anti-ITM2B antibody, we found APP and APLP2 proteins which have been previously described as ITM2B partners, notably playing a role in GABAb signaling in rodent brains[17,18]
Summary
ITM2B (Integral membrane protein 2b called BRI2, MIM#603904) is a single pass type II ubiquitous protein which function is still unclear. ITM2B is highly expressed in the brain and in the retina[3,4] Mutations in this gene lead to different disorders in humans. A Dan[8] and A Bri[5] are the major components of insoluble aggregates in the brain of affected subjects Another autosomal dominant mutation in ITM2B (c.782A>C, p.Glu261Ala) has been reported in an unusual retinal dystrophy associated with retinal ganglion cell abnormalities, inner retinal and cone dysfunctions. APP, APLP2 and ITM2B were found to form a complex interacting with G ABAb receptors in rodent b rains[17,18] Despite these published data, the molecular function of ITM2B remains mostly unknown and has never been studied in the retina. Our findings support a specific role for ITM2B in the retina and might suggest a role in the mitochondrial homeostasis
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