# Role of vesicular trafficking proteins in regulating centrosomes

> **NIH NIH R15** · NORTH CAROLINA AGRI & TECH ST UNIV · 2024 · $417,507

## Abstract

Role of endocytic proteins and membrane trafficking in regulating centrosomes
PROJECT SUMMARY/ABSTRACT
Centrosomes are comprised of a pair of cylindrical centrioles and associated pericentriolar matrix (PCM).
The major function of centrosomes is to organize a bipolar mitotic spindle to mediate accurate
chromosome partitioning. Centrosome dysfunction and abnormal centrosome numbers are associated
with diseases such as primary microcephaly and cancer. Hence, it is important to understand the cellular
mechanisms that regulate centrosome biology. Preliminary data from previous studies suggest roles for
membrane trafficking and endocytic proteins in regulating centrosome-related processes. However, our
understanding of how endocytic proteins and membrane trafficking orchestrate the numerical and
functional control of centrosomes is unknown. This proposal uses C. elegans as a model system to
elucidate the mechanisms by which the endocytic proteins dynamin (DYN-1 in C. elegans) and clathrin
(clathrin heavy chain is CHC-1 in C. elegans) and the process of vesicular trafficking regulate
centrosome function and number. The long-term goal is to understand how centrosomes are assembled
and how their function is regulated at the molecular level. The overall objectives in this application are to
shed light on the mechanism by which DYN-1, CHC-1, and vesicular trafficking function to mediate
proper PCM assembly and centrosome number. Our central hypothesis is that endocytic proteins and
vesicular trafficking regulate centrosome protein localizations and/or functions to ensure a properly built
and functioning centrosome. The rationale for this project is that although previous studies have
established a relationship between endocytosis and centrosome-related processes, our mechanistic
understanding of this relationship is limited. Our hypothesis will be tested by pursuing three specific aims:
1) Determine the mechanism by which DYN-1 inhibits excess SPD-2 recruitment to the centrosomes to
facilitate proper PCM assembly; 2) Determine if CHC-1 and ZYG-1 interact in vivo to mediate proper
centrosome duplication; and 3) Determine whether vesicular trafficking regulates the localization of the
important centrosome proteins AIR-1, PLK-1 and ZYG-1. We will utilize cell and molecular biology
techniques and C. elegans genetics to test our Specific Aims. The research proposed in this application
is innovative because we are the first to investigate the contribution of the endocytic proteins DYN-1 and
CHC-1 to centrosome biology in an in vivo model system. Developing therapeutic interventions for any
disease begins with understanding the fundamental mechanisms underlying disease-associated
processes at the level of basic science. The proposed research is significant because the dysregulation
of centrosome number and function is associated with a host of diseases, making a more comprehensive
understanding of how centrosome processes are regulated at the mechanistic level im...

## Key facts

- **NIH application ID:** 11290682
- **Project number:** 7R15GM152965-02
- **Recipient organization:** NORTH CAROLINA AGRI & TECH ST UNIV
- **Principal Investigator:** Jyoti Iyer
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $417,507
- **Award type:** 7
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11290682

## Citation

> US National Institutes of Health, RePORTER application 11290682, Role of vesicular trafficking proteins in regulating centrosomes (7R15GM152965-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11290682. Licensed CC0.

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