Spectrins: Molecular Organizers and Targets of Neurological Disorders

Overview

Journal Nat Rev Neurosci

Specialty Neurology

Date 2023 Jan 25

PMID 36697767

Authors

Damaris N Lorenzo

Reginald J Edwards

Anastasia L Slavutsky

Affiliations

Soon will be listed here.

Abstract

Spectrins are cytoskeletal proteins that are expressed ubiquitously in the mammalian nervous system. Pathogenic variants in SPTAN1, SPTBN1, SPTBN2 and SPTBN4, four of the six genes encoding neuronal spectrins, cause neurological disorders. Despite their structural similarity and shared role as molecular organizers at the cell membrane, spectrins vary in expression, subcellular localization and specialization in neurons, and this variation partly underlies non-overlapping disease presentations across spectrinopathies. Here, we summarize recent progress in discerning the local and long-range organization and diverse functions of neuronal spectrins. We provide an overview of functional studies using mouse models, which, together with growing human genetic and clinical data, are helping to illuminate the aetiology of neurological spectrinopathies. These approaches are all critical on the path to plausible therapeutic solutions.

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