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Investigating the Role and Regulation of the MAP7 Family Proteins in Axonal Morphogenesis and Function

Award Number: R01NS112504
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Investigating the Role and Regulation of the MAP7 Family Proteins in Axonal Morphogenesis and Function - PROJECT ABSTRACT Microtubules are protein polymers that are essential for neuronal cell morphogenesis during development. Microtubule assembly and function rely on the regulation of lattice-bound microtubule-associated proteins (MAPs). Many known MAPs influence microtubule stability and organelle transport, and some of them are highly associated with neurodegeneration. The proposed study will investigate a unique family of MAPs that interact with both microtubules and the motor protein kinesin-1. Our recent study of its founding member MAP7 provides the first demonstration of the neuronal function of this less-well understood MAP. MAP7 is developmentally regulated to promote axonal branch formation of sensory neurons in the dorsal root ganglion (DRG). Using primary neuronal cell culture, we have found that MAP7 regulates branch formation and growth. Further cell biological analysis has revealed that MAP7 regulates microtubule stability and kinesin-1-mediated organelle transport, two processes that are critical to axonal morphogenesis and function. Recently, we expand our studies in several directions. First, we analyzed another MAP7D1, a closest MAP7 homolog and found that it has similar properties and redundant function as MAP7 in culture. Second, we developed a new assay to show the potential role of MAP7 in regulating transport during branch growth. Third, in the study of MAP7 mouse mutants, we found a potential new role of MAP7 in nociception. Following these findings, we hypothesize that the MAP7 family proteins provide a novel mechanism and play multiple roles in axonal branch development and function by regulating organelle transport. To test this hypothesis, we ask three questions: 1) Are both MAP7/MAP7D1 required for branch development of DRG neurons? 2) How does MAP7 regulate organelle transport for branch growth and nociception? 3) is the nociception function specific for MAP7 expressed in DRG neurons and its interaction with kinesin-1? Answering these questions will not only expand our knowledge of this novel family of MAPs but also address fundamental questions regarding microtubule- based intracellular transport in neuronal development and function. More importantly, our proposed studies with a focus on DRG sensory neurons will allow us to explore the role of transport regulation in nociception and thus bring us closer to medically relevant problems, such as pain. Given the importance of nociception and pain in human health, our proposed studies with a focus on a fundamental cell biological problem are thus highly relevant to the NIH mission of investigating brain functions and disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $385,296 )
2025	2025	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/27/2024	NON-COMPETING CONTINUATION	$385,296
														Subtotal = $385,296

Issue Date FY: 2024 ( Subtotal = $415,263 )
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/25/2024	NON-COMPETING CONTINUATION	$29,967
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/26/2023	NON-COMPETING CONTINUATION	$385,296
														Subtotal = $415,263

Issue Date FY: 2023 ( Subtotal = $428,106 )
2023	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/8/2023	NON-COMPETING CONTINUATION	$428,106
														Subtotal = $428,106

Issue Date FY: 2022 ( Subtotal = $455,133 )
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/23/2022	NON-COMPETING CONTINUATION	$45,511
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/6/2021	NON-COMPETING CONTINUATION	$409,622
														Subtotal = $455,133

Issue Date FY: 2021 ( Subtotal = $428,106 )
2021	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/15/2020	NEW	$428,106
														Subtotal = $428,106

Grand Total All Awards = $2,111,904

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Investigating the Role and Regulation of the MAP7 Family Proteins in Axonal Morphogenesis and Function

Award Number: R01NS112504

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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