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

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2020 · $301,931

## 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
and function, and
a multi-system, multi-scale approach to understanding how
how these lead to changes in the function of MT networks
CTTs
impact
tubulin
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 five years has furthered our understanding of how -
tubulin CTTs regulate MT networks, and, more broadly, how tubulin heterogeneity impacts cellular and
developmental processes. The proposed project will build upon our expertise to expand the current model of
the tubulin code and give broader insights into mechanisms of MT function. Our goals for the next five years
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:** 9930294
- **Project number:** 1R35GM136253-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jeffrey Kyle Moore
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,931
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930294

## Citation

> US National Institutes of Health, RePORTER application 9930294, Beyond the tubulin code: Understanding how subunit diversity regulates the formation and function of microtubules (1R35GM136253-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9930294. Licensed CC0.

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