The Isotypes of α, β and γ Tubulin: From Evolutionary Origins to Roles in Metazoan Development and Ligand Binding Differences

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Background

Microtubules are built from heterodimers of α- and β-tubulin and are nucleated by γ-tubulin. α-, β-, and γ-tubulin each consists of isotypes, differing in amino acid sequence and encoded by different genes. The discovery of tubulin isotypes over four decades ago inspired two fundamentally different, but not mutually exclusive hypotheses: 1) isotypes encode functionally different tubulin proteins with potential for promoting specific microtubule architectures and activities in cells, and 2) isotypes encode functionally similar proteins but provide cells with transcriptional modules to meet shifting demands for tubulin during development and differentiation. Testing these hypotheses has proven to be a challenge for the field. Pioneering studies have given insights into the roles of isotypes in model organisms, and recent studies have linked isotype-specific mutations in human patients to roles in brain development and disease, for example in cancer. In addition, new technologies for targeted genome editing of specific isotypes in organisms and cultured cells, along with recombinant expression and purification of isotype-specific tubulin heterodimers provide opportunities to unlock long-standing mysteries in tubulin biology.

The goal of this collection is to assess current support for the above hypotheses, including functional differences between α, β, and γ tubulin isotype proteins and the roles of isotype expression in metazoan development and disease. We seek to highlight new insights into tubulin isotypes and to bring attention to remaining challenges and unanswered questions including specificity and selectivity of small molecules with respect to their affinity for tubulin isotypes. Answering some of these basic science questions may help in the design and development of more efficacious chemotherapy agents.

We seek research articles, reviews and manuscripts describing novel methods related to the following:

1) Describe the molecular diversity of α, β, and γ tubulin isotypes across eukaryotic evolution, and highlight structural features that promote differences in biochemical activity and function.

2) Review our current understanding of isotype conservation across species, and cell-type and developmental expression.

3) Present new research that advances our understanding of the roles of α, β, and γ tubulin isotypes in organisms.

4) Identify important frontiers in the field of tubulin isotypes.

5) Discuss the differences in the mechanisms of binding to tubulin isotypes by various classes of small molecule compounds, both standard and novel, which can be used as anti-mitotic agents.

Keywords: cytoskeleton, microtubule, tubulin, mitosis, brain development

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