# Cell type-specific roles of calpain-2 in formation of peripheral myelinated nerves

> **NIH NIH R03** · WRIGHT STATE UNIVERSITY · 2020 · $75,000

## Abstract

Project summary/abstract
 Both Schwann cells and neurons are essential for the formation of myelinated nerve fibers in the
peripheral nervous system (PNS). In addition to the electrical insulation of axons by myelin sheaths, Schwann
cells assemble nodes of Ranvier, the excitable axonal domains required for rapid and efficient action potential
propagation. Furthermore, Schwann cells actively modulate PNS degeneration and regeneration. However, the
cellular and molecular mechanisms of how these structures are formed, maintained, and disrupted in disease
conditions remain poorly understood. This critical gap in knowledge limits the field’s ability to manipulate the
Schwann cells and neurons for treatment of PNS diseases and injuries. The overall objective of this application
is to identify a critical molecular mechanism in the process of PNS myelinated nerve formation and injury. The
prior studies and preliminary data provided here have identified activation of calpains, calcium-dependent
intracellular cysteine proteases, and elevation of calpain-2 levels are involved in these processes. The
constitutive knockout of calpain-2 in mice results in embryonic lethality before myelin is formed, further
emphasizing the importance of calpain-2 in development of multiple organs including nervous system. The
central hypothesis is that calpain-2 modulates formation and injury of peripheral myelinated nerves. To begin to
test this hypothesis, this application will generate conditional knockout mice lacking calpain-2 in myelinating
Schwann cells (Aim 1) or in sensory neurons (Aim 2). Specific aim one will test the hypothesis that Schwann
cell calpain-2 mediates PNS myelination. Specific aim two will test the hypothesis that axonal calpain-2
modulates PNS node of Ranvier structures. Myelin and nodal structures in PNS, nerve conduction along PNS
myelinated axons, and animal behavior will be examined during postnatal development and in adult conditional
knockout and control mice. This application is conceptually innovative, in that we propose that calpain-2 is a
key modulator of myelinated nerve formation in PNS. This application will generate novel calpain-2 conditional
knockout mice, which will be used in future studies to determine Schwann cell-specific or neuron-specific roles
of calpain-2 in PNS injury and repair. The proposed research is significant, because completion of the aims will
identify calpain-2 as a potential modulator of myelinated nerve formation and remodeling in the PNS.
Furthermore, future research, utilizing conditional knockout mice generated in this application, is expected to
uncover cell type-specific roles of calpain-2 in PNS injuries and will substantially impact future translational
research aimed at the development of novel therapies for a wide variety of PNS diseases and injuries.

## Key facts

- **NIH application ID:** 10011907
- **Project number:** 5R03NS112981-02
- **Recipient organization:** WRIGHT STATE UNIVERSITY
- **Principal Investigator:** Keiichiro Susuki
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,000
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011907

## Citation

> US National Institutes of Health, RePORTER application 10011907, Cell type-specific roles of calpain-2 in formation of peripheral myelinated nerves (5R03NS112981-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011907. Licensed CC0.

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