Thursday, November 21, 2024 11/21/2024

Membrane Curvature Sensing Mechanisms for Synaptic Vesicle Endocytosis

Award Number: R01NS115974
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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Project Summary Endocytosis plays a crucial role in supporting the health of the human brain. Functionally, synaptic vesicle endocytosis allows neurons to sustain synaptic transmission without exhausting the supply of synaptic vesicles. Structurally, endocytosis supports the maintenance of synapses and neural circuits. As a result, defective synaptic vesicle endocytosis creates deficits in neurotransmission that underlie a wide spectrum of neurological diseases and psychiatric disorders. The long-term goal of this study is to determine how endocytic proteins act in concert to support diverse routes of endocytosis at synapses. Work from several laboratories including my own has found that the curvature-sensing protein endophilin plays a critical role in synaptic vesicle endocytosis. In this proposal, we will examine the hypothesis that curvature-sensing mechanisms guide endocytic proteins to perform their function in various routes of endocytosis. We propose three Specific Aims. 1) We will determine the role of curvature-sensing motifs in vivo. We focus on the curvature-sensing amphipathic helix of endophilin as it is essential for synaptic vesicle endocytosis. 2) We will study how curvature signals are received by the downstream protein synaptojanin to support synaptic vesicle endocytosis, and to prevent age-dependent decay of synaptic transmission. 3) We will determine the mechanism of endophilin-independent endocytosis, an area that lacks molecular information. Through an unbiased genetic screen, we have identified another curvature-sensing protein that acts in a parallel pathway with endophilin. Results from these studies are expected to to push boundaries of current knowledge of synaptic biology and to lead toward solutions for neurological 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: 2024 ( Subtotal = $460,290 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	2/2/2024	NON-COMPETING CONTINUATION	$427,075
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	4/10/2024	NON-COMPETING CONTINUATION	$118,747
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	2/5/2024	SUPPLEMENT FOR EXPANSION	$88,175
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	2/9/2024	SUPPLEMENT FOR EXPANSION	-$88,175
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	6	4/18/2024	NON-COMPETING CONTINUATION	-$85,532
														Subtotal = $460,290

Issue Date FY: 2023 ( Subtotal = $605,479 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	007	5	2/6/2023	SUPPLEMENT FOR EXPANSION	$59,796
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	008	5	9/8/2023	SUPPLEMENT FOR EXPANSION	-$17,318
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	5	1/27/2023	NON-COMPETING CONTINUATION	$474,826
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	5	2/3/2023	SUPPLEMENT FOR EXPANSION	$88,175
2023	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	4	11/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$247,673
2023	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	11/28/2022	SUPPLEMENT FOR EXPANSION	-$28,853
2023	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	11/28/2022	SUPPLEMENT FOR EXPANSION	-$22,711
2023	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	11/28/2022	NON-COMPETING CONTINUATION	-$89,755
2023	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/28/2022	NON-COMPETING CONTINUATION	-$106,354
														Subtotal = $605,479

Issue Date FY: 2022 ( Subtotal = $690,809 )
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	6/14/2022	NON-COMPETING CONTINUATION	-$337,851
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	008	4	6/22/2022	SUPPLEMENT FOR EXPANSION	$98,663
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	4	6/17/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$337,850
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	009	4	8/23/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$47,513
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	007	4	6/20/2022	SUPPLEMENT FOR EXPANSION	$65,464
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/19/2022	SUPPLEMENT FOR EXPANSION	$88,175
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	3	6/14/2022	SUPPLEMENT FOR EXPANSION	-$65,464
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	1/20/2022	SUPPLEMENT FOR EXPANSION	$127,516
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	3	6/14/2022	SUPPLEMENT FOR EXPANSION	-$98,663
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/17/2022	NON-COMPETING CONTINUATION	$427,606
														Subtotal = $690,809

Issue Date FY: 2021 ( Subtotal = $603,786 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/3/2021	NON-COMPETING CONTINUATION	$603,786
														Subtotal = $603,786

Issue Date FY: 2020 ( Subtotal = $555,680 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/12/2020	NEW	$485,941
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	8/4/2020	SUPPLEMENT FOR EXPANSION	$69,739
														Subtotal = $555,680

Grand Total All Awards = $2,916,044

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Membrane Curvature Sensing Mechanisms for Synaptic Vesicle Endocytosis

Award Number: R01NS115974

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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