# Supplement for Unraveling the molecular events driven by CaMKII in Ca2+-coupled cells

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2024 · $29,679

## Abstract

PROJECT SUMMARY
Cell to cell communication is critical for function in all multicellular organisms. A key factor for intercellular
communication is regulation by Ca2+ concentration. Ca2+/calmodulin dependent protein kinase II (CaMKII) is a
Ca2+ sensitive enzyme that is encoded by four genes in mammals: α, β, γ, and δ. There is an incredible amount
of diversity generated from the four vertebrate CaMKII genes. Alternative splicing produces up to 386 transcripts,
which leads to the production of 386 proteins that are then differentially post-translationally modified, and mix to
form hetero-oligomeric complexes, ultimately culminating in thousands of chemically distinct CaMKII
proteoforms. We are specifically interested in the crucial roles CaMKII plays in long-term memory formation
(neurons: α, β), fertilization (oocytes: γ), and cardiac physiology (cardiomyocytes: δ). Intriguingly, these cells all
communicate using Ca2+ oscillations but on vastly different timescales (minutes to milliseconds). How does one
enzyme accommodate this multifunctionality? We hypothesize that selective splicing and modification creates a
unique set of CaMKII variants expressed in specific cell types, thereby leading to differential functional outputs.
Fully elucidating these complex biological roles requires a deeper understanding of CaMKII variation at the
sequence and protein level, structural and conformational ramifications of these variations, and how these
variables affect CaMKII interactions within the cell. In this proposal, we seek to expand our understanding of
CaMKII function inside cells using a combinatorial approach of sequencing, biochemistry, structural biology, and
cellular assays. Completion of the proposed work will allow us to uncover the molecular basis for the many roles
of CaMKII in neurons, cardiomyocytes, and oocytes – with far-reaching implications on therapeutic intervention
for neurologic disease, cardiac dysfunction, and infertility.

## Key facts

- **NIH application ID:** 10979253
- **Project number:** 3R35GM145376-02S1
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Margaret M Stratton
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $29,679
- **Award type:** 3
- **Project period:** 2022-09-24 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979253

## Citation

> US National Institutes of Health, RePORTER application 10979253, Supplement for Unraveling the molecular events driven by CaMKII in Ca2+-coupled cells (3R35GM145376-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10979253. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*