# The role of the microtubule-binding protein WDR73 in mitotic and post-mitotic cells

> **NIH NIH R15** · FRANKLIN AND MARSHALL COLLEGE · 2020 · $386,771

## Abstract

A strong understanding of cell cycle, the process through which cells grow and divide in a controlled manner to
promote the growth of organisms, is vital to our understanding of healthy human development, developmental
disorders, and cancers. We recently described a novel protein, WDR73, as a microtubule-interacting protein
important during mitosis (cell division). We associated WDR73 gene mutations with Galloway-Mowat Syndrome
(GAMOS), a rare, recessive developmental disorder characterized by microcephaly, reduced growth of the
cerebellum, intellectual disability, growth retardation, blindness, kidney disease and untimely death. Our
research determined that WDR73 is required for normal progression through cell cycle, especially mitosis. During
mitosis, WDR73 localizes to the microtubules as they form the mitotic spindles and stays with them as they grow
to capture the chromosomes during prometaphase and metaphase. WDR73 remains at the spindles during
anaphase (segregation of chromosomes) but also extends into the interpolar and kinetochore microtubules until
telophase when it concentrates at the midbody microtubules, where final separation of the daughter cells
(cytokinesis) is coordinated. The goal of this proposal is to investigate the function of WDR73 during all phases
of cell cycle and neuronal differentiation. Based on preliminary data on WDR73’s interactions with other proteins,
we hypothesize that WDR73 scaffolds dynamic protein interactions during multiple phases of cell cycle and sub-
phases of mitosis. During mitosis, preliminary data suggest that WDR73 may play a role in the nucleation and
stabilization of mitotic microtubules. Our studies of GAMOS patient cells further suggest that WDR73 may be
required for cell survival, normal timing of exit from cell cycle, and cell differentiation. We will use cell biological
and biochemical approaches to investigate these hypotheses through three Specific Aims: (1) Determine the
role of WDR73 in the assembly and remodeling of mitotic and interphase microtubule networks. Live and
fixed cell imaging will be used in GAMOS patient cells and in cell lines in which WDR73 will be depleted by RNA
interference (gene silencing) to determine how loss of WDR73 function impairs microtubule networks and delays
cell cycle. (2) Characterize the WDR73 protein interactome in proliferating and non-proliferating
(differentiated) cells. Unbiased co-immunoprecipitation and mass-spectrometry will be used during each phase
of cell cycle and sub-phase of mitosis, and in post-mitotic neurons to identify novel WDR73 interacting proteins.
(3) Investigate the role of WDR73 in neuronal differentiation and survival. RNA interference will be used to
assess the impact of loss of WDR73 protein on proliferation, survival, and differentiation of neural cells. This
research is innovative because it aims to characterize the function of a novel protein required for proper
progression through cell cycle. It is significant because it ...

## Key facts

- **NIH application ID:** 10046529
- **Project number:** 1R15GM139134-01
- **Recipient organization:** FRANKLIN AND MARSHALL COLLEGE
- **Principal Investigator:** Robert Nelson Jinks
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,771
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046529

## Citation

> US National Institutes of Health, RePORTER application 10046529, The role of the microtubule-binding protein WDR73 in mitotic and post-mitotic cells (1R15GM139134-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10046529. Licensed CC0.

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