# Role of Vesicular Trafficking Proteins in Regulating Centrosomes

> **NIH NIH R15** · UNIVERSITY OF TULSA · 2024 · $3,793

## Abstract

Role of vesicular trafficking proteins in regulating centrosomes
PROJECT SUMMARY/ABSTRACT
Centrosomes are comprised of a pair of cylindrical centrioles and associated pericentriolar material
(PCM). Their major function 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. Previous studies have revealed that a centrosome-associated
membrane structure called the centriculum plays a critical role in regulating centrosome function.
However, the mechanism by which membranes and membrane-associated proteins regulate
centrosomes is unknown. Prior studies have suggested roles for the membrane-associated endocytic
proteins clathrin and dynamin in regulating centrosome number and PCM assembly, respectively.
However, our understanding of the mechanism by this occurs is unclear. This proposal uses C. elegans
as a model system to elucidate how the vesicular trafficking proteins clathrin (clathrin heavy chain is
CHC-1 in C. elegans) and dynamin (DYN-1 in C. elegans) regulate centrosomes. Our long-term goal is to
understand how membranes and membrane-associated proteins regulate centrosome biology. The
overall objectives in this application are to understand how the membrane-associated endocytic proteins
CHC-1 and DYN-1 collaborate with the core centrosome proteins ZYG-1 and SPD-2, respectively to
regulate centrosome number and PCM assembly. Our central hypothesis is that CHC-1 and DYN-1
regulate ZYG-1 and SPD-2 protein localizations respectively, either in an endocytosis-dependent or in an
endocytosis-independent manner to ensure a properly built and functioning centrosome. Our hypothesis
will be tested by pursuing two specific aims: 1) Determine the mechanism by which CHC-1 and ZYG-1
interact and elucidate the effect of perturbing this interaction on centrosome duplication and ZYG-1
localization. 2) Test the hypothesis that DYN-1 plays a critical role in PCM assembly by controlling the
amount of SDP-2 recruitment via vesicular trafficking. 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 membrane-associated vesicular
trafficking proteins CHC-1 and DYN-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 imperative.

## Key facts

- **NIH application ID:** 10974077
- **Project number:** 1R15GM152965-01A1
- **Recipient organization:** UNIVERSITY OF TULSA
- **Principal Investigator:** Jyoti Iyer
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,793
- **Award type:** 1
- **Project period:** 2024-07-01 → 2024-08-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974077

## Citation

> US National Institutes of Health, RePORTER application 10974077, Role of Vesicular Trafficking Proteins in Regulating Centrosomes (1R15GM152965-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10974077. Licensed CC0.

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