NIH RESEARCH GRANT: Presynaptic cytomatrix proteins and synaptogenesis

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Grant Number: 5P01HD038760-030001

PI Name: GARNER, CRAIG C.

PI Email: garner@...

PI Title: PROFESSOR

Project Title: Presynaptic cytomatrix proteins and synaptogenesis

Abstract: Synapses of the mammalian CNS are highly specialized cellular

junctions designed for rapid and regulated signaling between nerve cells and

their targets. Abnormal synaptogenesis and synaptic reorganization in the

developing CNS has been strongly correlated with developmental disorders

such as fragile X, epilepsy, schizophrenia and mental retardation. Our

ability to understand how different genetic and environmental insults cause

cognitive dysfunction and mental retardation requires a better understanding

of the cellular mechanisms that lead to the proper assembly and function of

CNS synapses. This requires a molecular description of the constituents of

synaptic junctions and the mechanisms used by neurons to correctly sort

traffic and localized each component. Our studies of CNS synapses have led

to the identification and characterization of numerous synaptic junctional

proteins. One of the most recently identified, Bassoon, is a novel component

of the presynaptic cytoskeletal matrix assembled at the active zone. Based

on its structure on its structure and distribution, we hypothesize that it

is involved in the assembly and function of CNS synapses. With regard to

mental retardation and cognitive dysfunction, our analysis of the Bassoon

gene and its transcripts have revealed the presence of a CAG expansion

similar to these found Huntingtin, Ataxins and the Fragile X mental

retardation Moreover, Basson expression is selectively enhanced in a

neurodegenerative disorder, multiple system atrophy. To gain insights into

the role played by Bassoon in the presynaptic cytoskeletal matrix, we

proposed to examine the mechanisms directing that transport and assembly of

Bassoon at CNS synapses In addition we propose to assess the function of

Bassoon in presynaptic nerve terminals by analyzing loss of function

mutations in the mouse Bassoon gene Bsn on the structure, assembly, and

function of CNS synapses in the developing mouse brain.

Thesaurus Terms:

nerve /myelin protein, neuronal transport, protein localization, protein

structure function, synaptogenesis

gene expression, molecular assembly /self assembly, protein transport

embryo /fetus cell culture, laboratory mouse, laboratory rat, tissue /cell

culture

Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM

UAB STATION

BIRMINGHAM, AL 35294

Fiscal Year: 2002

Department:

Project Start:

Project End:

ICD: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

IRG: CHHD