The role of the integral type II transmembrane protein BRI2 in health and disease

Cell Mol Life Sci. 2021 Nov;78(21-22):6807-6822. doi: 10.1007/s00018-021-03932-5. Epub 2021 Sep 4.

Abstract

BRI2 is a type II transmembrane protein ubiquitously expressed whose physiological function remains poorly understood. Although several recent important advances have substantially impacted on our understanding of BRI2 biology and function, providing valuable information for further studies on BRI2. These findings have contributed to a better understanding of BRI2 biology and the underlying signaling pathways involved. In turn, these might provide novel insights with respect to neurodegeneration processes inherent to BRI2-related pathologies, namely Familial British and Danish dementias, Alzheimer's disease, ITM2B-related retinal dystrophy, and multiple sclerosis. In this review, we provided a state-of-the-art outline of BRI2 biology, both in physiological and pathological conditions, and discuss the proposed molecular underlying mechanisms. Overall, the BRI2 knowledge here reviewed is of extreme importance and may contribute to propose BRI2 and/or BRI2 proteolytic fragments as novel therapeutic targets for neurodegenerative diseases, such as Alzheimer's disease.

Keywords: BRI2; Neurodegeneration; Neuronal differentiation; Protein phosphorylation; Regulated intramembrane proteolysis; Synaptic transmission.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Animals
  • Humans
  • Membrane Proteins / metabolism*
  • Proteolysis
  • Signal Transduction / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins