# Mechanisms of Spatial Organization in the Cytoplasm

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2022 · $398,108

## Abstract

Cell polarity is fundamental to the biology of most cells and is characterized by
the asymmetric distribution of factors at the cell cortex (the region just beneath the
plasma membrane) and in the cytoplasm. A conserved set of proteins, the PAR
(PARtitioning defective) proteins regulate polarity in most polarized animal cells. While
we know a great deal about how they generate cortical asymmetries, little is known about
how cortical PAR proteins segregate diffusive proteins in the cytoplasm. In the C.
elegans zygote, the PAR proteins localize to two complementary domains at the cell
cortex from which they orchestrate cellular polarities. The posterior kinase PAR-1 drives
the segregation of the essential protein MEX-5 to the anterior cytoplasm. In turn, MEX-5
drives the segregation of germ line determinants (collectively, the germ plasm) to the
anterior cytoplasm. The conserved mitotic kinase PLK-1 is recruited by MEX-5 to the
anterior cytoplasm and is important for germ plasm segregation. We recently found that
PLK-1 phosphorylates one germ plasm protein, POS-1, to inhibit its retention in the
anterior, thereby driving its segregation to the posterior. In the proposed work, we will
identify additional substrates of PLK-1 that mediate germ plasm segregation. In addition,
we will determine the role of the endoplasmic reticulum and mitochondrial networks in
scaffolding cytoplasmic asymmetries. Because the core polarity regulators are conserved,
knowledge of the principles and mechanisms that establish asymmetries in the C.
elegans zygote will provide a foundation for understanding how asymmetries are
generated in human cells.

## Key facts

- **NIH application ID:** 10410359
- **Project number:** 5R35GM136302-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** ERIK E GRIFFIN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,108
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410359

## Citation

> US National Institutes of Health, RePORTER application 10410359, Mechanisms of Spatial Organization in the Cytoplasm (5R35GM136302-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10410359. Licensed CC0.

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