# In vivo functional analysis of a neuronal membrane-specific proteasome complex

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $532,125

## Abstract

Homeostatic control of neuronal activity, which maintains activity levels within a
functional range, is critical for the stability of neuronal circuits and normal brain
functions. Yet the underlying mechanisms governing homeostatic control of neuronal
activity levels remain largely unknown. Emerging evidence suggests that proteostasis,
especially the synthesis and degradation of activity-induced newly-synthesized proteins,
may be involved in the regulation of activity homeostasis in neurons. The recent
discovery and initial characterization of a neuronal membrane specific proteasome
(NMP) suggests that NMPs preferentially degrade activity-induced newly-synthesized
proteins and that NMP function influences neuronal activity. Together, these in vitro
studies suggest a potential protein-degradation based regulatory mechanism for
neuronal homeostasis, however evidence for in vivo functions of the NMP are lacking,
particularly whether the NMP degrades newly-synthesized proteins, whether NMP
activity affects neuronal activity levels and circuit function and whether in vivo NMP
substrates can be identified. Here, we propose to investigate the function of the NMP in
vivo in the visuomotor circuit of Xenopus laevis tadpoles. First, we will determine
whether NMPs are present in optic tectal neurons of tadpoles and assess NMPs
proteolytic activity for activity-induced newly-synthesized or pre-existing proteins in vivo.
Then we will examine the interaction between NMP activity and neuronal activity using
in vivo functional Ca imaging, and the influence of NMP function on visuomotor
behavioral plasticity in intact animals. Finally, we will quantify changes of individual
proteins to identify NMP substrates under basal and stimulated conditions. Results of
these studies will begin to establish NMP functions in vivo and to assess the potential
function of NMP-mediated protein degradation in the maintenance of neuronal and
circuit homeostasis.

## Key facts

- **NIH application ID:** 9877548
- **Project number:** 1R21NS114975-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** HOLLIS T. CLINE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $532,125
- **Award type:** 1
- **Project period:** 2019-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877548

## Citation

> US National Institutes of Health, RePORTER application 9877548, In vivo functional analysis of a neuronal membrane-specific proteasome complex (1R21NS114975-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9877548. Licensed CC0.

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