# Role of DYRK1A/MNB in synaptic growth and function

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $442,345

## Abstract

Following neurotransmitter release, synaptic vesicle membrane and protein components are rapidly retrieved
from the plasma membrane through endocytosis, and functional synaptic vesicles are subsequently
regenerated from the endocytosed components. This fundamental process, called synaptic vesicle recycling,
is crucial for sustaining neuronal communication across a wide range of neuronal activities. Impaired synaptic
vesicle recycling can thus deleteriously affect neuronal survival and function, and is associated with numerous
neurological disorders. There are multiple modes of synaptic vesicle endocytosis, including clathrin-mediated
endocytosis and clathrin-independent bulk endocytosis. While it is widely known that dynamic phosphorylation
of synaptic proteins by kinases delicately regulates clathrin-mediated endocytosis, mechanisms modulating
clathrin-independent bulk endocytosis are not well understood. In this proposal, will use Drosophila
melanogaster, which offers the advantage of powerful genetics and well-characterized glutamatergic synapses
at the neuromuscular junction, to investigate the functions of a synaptic kinase called Minibrain (MNB), also
known as DYRK1A, in regulating multiple steps of synaptic vesicle recycling. We will take a multidisciplinary
approach combining genetics, biochemistry, cell biology, and electrophysiological analyses to address the role
of MNB/DYRK1A in clathrin-independent bulk endocytosis and synaptic vesicle regeneration. We will address
the following questions in this proposal: 1) what is the role of MNB/.DYRK1A in regulating clathrin-independent
bulk endocytosis? 2) Does MNB regulate bulk endocytosis through phosphorylation of Synaptojanin, a
previously identified synaptic target of MNB? 3) Is MNB required for the recovery of functional synaptic
vesicles pools? 4) What is the mechanism by which MNB regulates functional recovery of synaptic vesicles?
As MNB/DYRK1A is upregulated in Down syndrome and mutated in some cases of Autism, a thorough
understanding of MNB functions at the synapse will provide novel insights into mechanisms underlying
neurological disorders and contribute to therapeutic development in the future.

## Key facts

- **NIH application ID:** 9944686
- **Project number:** 5R01NS080946-08
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** KAREN T CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,345
- **Award type:** 5
- **Project period:** 2013-07-16 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944686

## Citation

> US National Institutes of Health, RePORTER application 9944686, Role of DYRK1A/MNB in synaptic growth and function (5R01NS080946-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9944686. Licensed CC0.

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