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Molecular Mechanisms of Active Zone Formation at Drosophila Synapses

Award Number: R15NS087601
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2014
PERIOD OF PERFORMANCE END DATE: 02/28/2018

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Molecular Mechanisms of Active Zone Formation at Drosophila Synapses - DESCRIPTION (provided by applicant): Our long term goal is to identify the molecular mechanisms that control the formation and modulation of synapses. These mechanisms control the assembly of pre- and post- synaptic components required for proper synaptic function and ensure their appropriate apposition across the synaptic cleft. Regulation of such mechanisms controls synaptic plasticity and the processes that underlie the neural basis of learning and memory, and defects in these mechanisms are likely causes of neurodevelopmental and neurodegenerative disease. The Drosophila neuromuscular junction (NMJ) is a powerful model for studying synapse formation and function. Each NMJ is composed of hundreds of presynaptic release sites, or active zones, which are directly apposed to clusters of postsynaptic receptors in the muscle membrane. Proteins that compose the presynaptic release machine cluster at each presynaptic active zone to regulate efficient vesicle release. The mechanisms that control the accumulation of release machinery proteins at active zones remain unclear, but the protein Rab3 has recently been identified as playing a novel role that controls the localization of the presynaptic release machine to synapses. In the Drosophila rab3 mutant, the majority of release sites are devoid of presynaptic proteins required for efficient vesicle release. However the mechanism by which Rab3 controls the accumulation of release machinery proteins to active zones is unknown. In an RNAi screen to identify genes that interact with Rab3 to control active zone formation, three RNAi lines were identified that enhance or suppress the rab3 mutant phenotype. The proteins disrupted by these RNAi lines along with mutants of genes known to interact with Rab3 will be studied to determine the molecular mechanisms that control active zone development and synapse formation.


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: 2018 ( Subtotal = -$37,548 )
2018	2014	AMHERST COLLEGE, TRUSTEES OF	103 CONVERSE HALL	AMHERST	MA	01002	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/13/2018	NEW	-$37,548
														Subtotal = -$37,548

Issue Date FY: 2014 ( Subtotal = $371,823 )
2014	2014	TRUSTEES OF AMHERST COLLEGE	P.O. BOX 5000	AMHERST	MA	01002	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/10/2014	NEW	$371,823
														Subtotal = $371,823

Grand Total All Awards = $334,275

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Molecular Mechanisms of Active Zone Formation at Drosophila Synapses

Award Number: R15NS087601

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2014

PERIOD OF PERFORMANCE END DATE: 02/28/2018

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