# Investigating the molecular mechanisms of early neuronal morphogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2023 · $46,997

## Abstract

SUMMARY
Cellular morphology is one of the most distinctive features of somatic cells in multicellular organisms and is
intimately linked with cellular function. How neurons and other polarized cells commit to their morphologies is
poorly understood, but spontaneous morphogenesis of dissociated cells in culture suggest that the basic
instructions for morphology are often intrinsically encoded. We previously identified a sequence-specific RNA-
binding protein, Unkempt, as a factor that is essential for the establishment of the early neuronal morphology
and as a protein that is capable of endowing a similar shape to cells of nonneuronal origin. Unkempt
recognizes a unique binding motif predominantly within coding regions mRNAs the translation of which it
suppresses. It is unclear how Unkempt regulates translation, and whether translation or another functional
modality of Unkempt is critical to its induction of cell polarization. Here, we seek to solve this problem by
deciphering the mechanistic basis of Unkempt-driven remodeling of cellular shape. Our preliminary studies
indicate that in the broad protein-protein interaction network of Unkempt, the interaction between Unkempt’s
low-complexity domain (LCD) and the CCR4-NOT complex is exquisitely required for the induction of cell
morphogenesis. We propose three specific aims to investigate the molecular and cellular roles of the CCR4-
NOT complex as a critical effector of Unkempt-controlled cell morphogenesis. First, we will investigate the
nature of Unkempt – CCR4-NOT interactions and their impact on the fate of the targeted messages, focusing
in particular on their poly(A) tail length, stability, and translation. Second, we will interrogate the recruitment
and function of CCR4-NOT in Unkempt-induced cell morphogenesis. Third, we will determine the effect of
post-translational modifications of Unkempt on its interactions with the CCR4-NOT complex and RNA, as well
as its control of local protein translation. This study will shed light on the molecular underpinnings of the early
neuronal morphogenesis and contribute to our general understanding of the cues that control cellular
morphology in development and disease.

## Key facts

- **NIH application ID:** 10795510
- **Project number:** 3R01GM144693-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Jernej Murn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $46,997
- **Award type:** 3
- **Project period:** 2023-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795510

## Citation

> US National Institutes of Health, RePORTER application 10795510, Investigating the molecular mechanisms of early neuronal morphogenesis (3R01GM144693-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10795510. Licensed CC0.

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