# Molecular mediators of muscle spindle mechanosensation

> **NIH NIH R16** · SAN JOSE STATE UNIVERSITY · 2024 · $146,500

## Abstract

PROJECT SUMMARY: Molecular mediators of muscle spindle
mechanosensation.
Many conditions, including aging, chemotherapy-induced peripheral neuropathy, and neuromuscular diseases,
negatively impact the function of muscle proprioceptors. The Group Ia and II muscle spindle afferents are
slowly-adapting mechanoreceptors and provide the primary sensory information for proprioception and
comprise the sensory arm of the muscle stretch reflex. The exact molecular mechanism used to translate
muscle stretch into action potentials in these neurons is only incompletely understood. However, the
mechanically gated ion channel PIEZO2 is known to be necessary for normal stretch sensitivity and multiple
genetic diseases that increase or decrease PIEZO2 channel function are known to impair proprioception and
motor behaviors. The voltage gated sodium channel NaV1.1 and vesicle-released glutamate are also known to
be necessary for maintained excitability during static stretch. The overarching goal of this proposal is to
understand how the developmental timing of dysfunction in those proteins alters muscle spindle afferent
mechanosensation. We will determine how a mouse model with a gain of function mutation to Piezo2 which
leads to Distal Arthrogryposis Type 5 alters mechanosensation in the muscle spindle afferents when it is
expressed throughout development or only after the muscle spindle is developed (Aim 1). Similarly, we will
determine whether loss of Piezo2 once the muscle spindle develops eliminates stretch sensitive firing as it
does following constitutive loss. We will also use a model of Angelman Syndrome that decreases Piezo2
channel activity to determine how mechanosensation is impaired under a less complete decrease in Piezo2
function (Aim 2). Finally, we will determine whether loss of NaV1.1 after the muscle spindle has developed
leads to similar inconsistent static phase firing as observed following constitutive loss and whether NaV1.1
and/or vesicle-released glutamate are less important for mediating the more rapidly-adapting stretch responses
seen before the muscle spindle matures (Aim 3). These results will increase understanding of how alteration in
the function of key components of the muscle spindle afferent mechanotransduction machinery affect function
during genetic disorders or other later-onset disease states that target these molecular mediators.

## Key facts

- **NIH application ID:** 10848832
- **Project number:** 1R16GM153600-01
- **Recipient organization:** SAN JOSE STATE UNIVERSITY
- **Principal Investigator:** Katherine Anne Wilkinson
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $146,500
- **Award type:** 1
- **Project period:** 2024-03-18 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848832

## Citation

> US National Institutes of Health, RePORTER application 10848832, Molecular mediators of muscle spindle mechanosensation (1R16GM153600-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848832. Licensed CC0.

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