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Mechanism and Synaptic Function of Binding Between Proteins Kirrel3 and IgSF8

Award Number: F31MH134619
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Mechanism and Synaptic Function of Binding Between Proteins Kirrel3 and IgSF8 - Abstract Targeting and functional specificity of synapses rely on a complicated network of protein interactions. Trans- synaptic adhesion through cell surface proteins is one type of protein interaction that is required for synapse formation. Neurons express multiple synaptic cell surface proteins but little is known about how they interact with one another. This is important because many neurodevelopmental disorders are associated with altered surface protein expression. Kirrel3 is a cell surface and synaptic adhesion protein from the immunoglobulin superfamily and Kirrel3 is necessary to form mossy fiber filopodia synapses that connect dentate gyrus neurons to GABAergic neurons in the hippocampus. To elucidate the mechanism of Kirrel3 function at this synapse, I conducted a proteomic screen to identify Kirrel3 binding partners. One protein I identified is another Ig superfamily member called IgSF8. IgSF8 was also shown to be necessary for mossy fiber filopodia formation but how Kirrel3 and IgSF8 work together in constructing this synapse is unknown. In two aims, I will determine how Kirrel3 and IgSF8 physically interact and if the synaptogenic function of Kirrel3 depends on IgSF8. My results will advance the understanding of mechanisms by which synaptic specificity is achieved and given that Kirrel3 variants have been identified as risk factors for neurodevelopmental disorders, my results have potential to address a cellular foundation contributing to human disease.


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 = $40,577 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Mental Health Research Grants	001	2	9/8/2025	NON-COMPETING CONTINUATION	$564
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Mental Health Research Grants	000	2	4/9/2025	NON-COMPETING CONTINUATION	$40,013
														Subtotal = $40,577

Issue Date FY: 2024 ( Subtotal = $40,013 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Mental Health Research Grants	001	1	3/7/2024	NEW	$0
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Mental Health Research Grants	000	1	3/7/2024	NEW	$38,733
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Mental Health Research Grants	002	1	8/2/2024	NEW	$1,280
														Subtotal = $40,013

Grand Total All Awards = $80,590

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Mechanism and Synaptic Function of Binding Between Proteins Kirrel3 and IgSF8

Award Number: F31MH134619

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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