A Crosslinking Mass Spectrometry Protocol for the Structural Analysis of Microtubule-Associated Proteins

Rafiei, Atefeh; Schriemer, David C.

doi:10.1007/978-1-0716-2124-0_14

Cited by 1 publication

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“…It is now possible to generate and characterise cerebral organoids from iPSC lines generated from patients with tubulin mutations, alongside CRISPR-repaired isogenic controls. Coupled with advanced quantitative proteomic methods, investigators can interrogate the effect of tubulin mutations on the microtubule proteome in a human system with greater ease ( Leca et al, 2020 ; Rafiei and Schriemer, 2022 ). This would permit the identification of novel MAPs relevant to disease states, as it likely there are numerous uncharacterised MAPs that have yet to be identified that influence microtubule behaviour in unexpected ways ( Jijumon et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

MAPping tubulin mutations

Cushion

Leca²,

Keays³

2023

Front. Cell Dev. Biol.

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Microtubules are filamentous structures that play a critical role in a diverse array of cellular functions including, mitosis, nuclear translocation, trafficking of organelles and cell shape. They are composed of α/β-tubulin heterodimers which are encoded by a large multigene family that has been implicated in an umbrella of disease states collectively known as the tubulinopathies. De novo mutations in different tubulin genes are known to cause lissencephaly, microcephaly, polymicrogyria, motor neuron disease, and female infertility. The diverse clinical features associated with these maladies have been attributed to the expression pattern of individual tubulin genes, as well as their distinct Functional repertoire. Recent studies, however, have highlighted the impact of tubulin mutations on microtubule-associated proteins (MAPs). MAPs can be classified according to their effect on microtubules and include polymer stabilizers (e.g., tau, MAP2, doublecortin), destabilizers (e.g., spastin, katanin), plus-end binding proteins (e.g., EB1-3, XMAP215, CLASPs) and motor proteins (e.g., dyneins, kinesins). In this review we analyse mutation-specific disease mechanisms that influence MAP binding and their phenotypic consequences, and discuss methods by which we can exploit genetic variation to identify novel MAPs.

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Section: Discussionmentioning

confidence: 99%