# The role of copines in the regulation of the actin cytoskeleton and membrane trafficking

> **NIH NIH R15** · CENTRAL MICHIGAN UNIVERSITY · 2022 · $99,998

## Abstract

PROJECT SUMMARY
 Copines are a family of calcium-dependent membrane binding proteins found in most eukaryotic organisms
including humans, which have nine different copine genes. Copines have been implicated in numerous human
cancers. However, at this time there is no unifying theme with respect to the function of these elusive proteins.
The main goal of this research project is to determine whether a common basic mechanistic function can be
attributed to all copine proteins. We have been using the model organism Dictyostelium discoideum to study
these enigmatic proteins. Dictyostelium is a good model organism to study these proteins because they have
six copines genes, while other model organisms either have a few or no copine genes. Our studies have
mostly focused on Copine A (CpnA). However, we now have many of the tools to study the other five copines
(CpnB-F). Our studies on cpnA knockout mutants in Dictyostelium indicate that CpnA is involved in many
cellular functions including processes that require the actin cytoskeleton (i.e. cytokinesis, chemotaxis, cell
polarity, and adhesion) and require membrane fusion (i.e. contractile vacuole expulsion, and postlysosome
maturation and exocytosis). Biochemical studies indicate that CpnA binds to acidic phospholipids and actin
filaments in a calcium-dependent manner. Localization studies indicate that CpnA is a soluble cytoplasmic
protein that translocates to the plasma membrane and the membranes of the contractile vacuole system and
organelles of the endolysosomal system in response to a rise in calcium concentration. Two main hypotheses
for the function of CpnA emerge from our studies: CpnA functions in the calcium-dependent regulation of 1)
actin filament dynamics and/or 2) membrane fusion. Therefore, we propose to use Dictyostelium to explore the
idea that all copines, from single-celled organisms to humans, are involved in the calcium-dependent
regulation of actin filament dynamics and/or membrane fusion. We plan to use several strategies that include
the functional characterization of copine knockout mutants and identification of copine protein binding partners.
Total Internal Reflection Fluorescence Microscopy (TIRF) will be used to visualize actin filament dynamics and
membrane fusion in the copine knockout mutants. We will also explore the more specific hypothesis that
copines regulate actin filaments on membrane surfaces to regulate membrane fusion. TIRF Microscopy is a
special type of fluorescence microscopy that restricts excitation and emission of fluorophores to a very thin
region of the specimen immediately adjacent to the glass coverslip and is used to image cellular processes
happening close to the plasma membrane. If we find that not all copines function in the regulation of actin
filament dynamics and/or membrane fusion, a unifying theme for copines will most likely emerge as we
characterize each of the copine knockout mutants to identify any common defects and identify common
bind...

## Key facts

- **NIH application ID:** 10581990
- **Project number:** 3R15GM078089-03S1
- **Recipient organization:** CENTRAL MICHIGAN UNIVERSITY
- **Principal Investigator:** CYNTHIA K DAMER
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $99,998
- **Award type:** 3
- **Project period:** 2008-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581990

## Citation

> US National Institutes of Health, RePORTER application 10581990, The role of copines in the regulation of the actin cytoskeleton and membrane trafficking (3R15GM078089-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10581990. Licensed CC0.

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