# Beyond the tubulin code: Understanding how subunit diversity regulates the formation and function of microtubules

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2023 · $13,253

## Abstract

Project Summary:
A fundamental question in cell biology is how cells build functionally and structurally distinct microtubule (MT)
networks using a seemingly simple set of protein building blocks -- -tubulin heterodimers. For many years,
the cytoskeletal field has focused on the roles of MT-binding proteins and motors as the primary regulators of
network structure and function. However, it is now clear that the -tubulin building blocks are not so simple.
Rather than a uniform track, the MT surface is a molecularly diverse landscape that is generated by genetic
and posttranslational differences between -tubulins. The `tubulin code' model posits that changes to the
intrinsically disordered carboxy-terminal tail (CTT) domains of -tubulins create a molecular code at the MT
surface that is “read” by MT-binding proteins. The overarching goals of this proposal are to establish
mechanistic connections between CTTs and the conformational diversity of MT ends and lattices, and to
understand how this regulates complex MT network functions at the cellular level.
This
structure
 proposal features a multi-system, multi-scale approach to understanding how CTTs impact tubulin
 and function, and how these lead to changes in the function of MT networks in cells. My lab has
established expertise in investigating tubulin using approaches that integrate genetic models, live-cell imaging
and protein biochemistry. Our progress over the past ten years has furthered our understanding of how -
tubulin CTTs regulate MT networks, and, more broadly, how tubulin heterogeneity impacts cellular and
developmental processes. This project builds upon our expertise to expand the current model of the tubulin
code and give broader insights into mechanisms of MT function. Our goals include 1) define how CTTs guide
the structure of MT ends to regulate MT dynamics, 2) determine how blends of -tubulins with different amino
acid sequences and posttranslational modifications give rise to complex behaviors at the level of MT networks
in cells, 3) define how CTTs promote the directionality of kinesin motility along MTs, and 4) establish a novel
role for tubulins in buffering intracellular cation concentrations. Our synergistic approach is uniquely suited to
advance knowledge of tubulin structure and function that will be important in a broad range of contexts, provide
new insights into how microtubule networks regulate and respond to changes at the level of tubulin subunits,
and how these impact different cellular contexts.

## Key facts

- **NIH application ID:** 10807889
- **Project number:** 3R35GM136253-04S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jeffrey Kyle Moore
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $13,253
- **Award type:** 3
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807889

## Citation

> US National Institutes of Health, RePORTER application 10807889, Beyond the tubulin code: Understanding how subunit diversity regulates the formation and function of microtubules (3R35GM136253-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10807889. Licensed CC0.

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