Post-transcriptional Regulation of Neurofilament Expression during Axon Outgrowth

Suny At Albany, Albany NY

Investigators

Abstract

Neurons communicate with each other by transmitting electrical impulses down a long cellular process called the axon. The central question of this project is how does a neuron coordinate the synthesis of the many structural proteins that are needed to make an axon during development? This coordination had long been thought to occur as genes are first read out (i.e., during transcription), but new information indicates that much of it also happens afterward, as the proteins themselves are being synthesized. Loss of a single protein that regulates protein synthesis, called hnRNP K, leads selectively to the loss of not only one of the most abundant axonal structural proteins (a neurofilament protein) but also of the entire axon. Because loss of neurofilaments does not normally lead to loss of entire axons, hnRNP K is hypothesized to be a global regulator of the synthesis of multiple structural proteins that cooperate in building the axon. The first objective of this project is to use high throughput biochemical assays to identify these proteins. The second objective is to use mutated versions of hnRNP K that can be visualized in living neurons to study how the actions of hnRNP K are regulated by cell signaling pathways during axon outgrowth. The potential impact of this work is to provide new insights into how neurons coordinate the expressions of multiple, functionally interrelated proteins during development. This project will provide research training for two PhD students and undergraduates at a public institution with a culturally diverse student body. Spinoffs from this work will have an impact on undergraduate student laboratory exercises in Developmental Biology and on courses taught by the PI in Molecular Biology, Developmental Neurobiology, and Molecular Neurobiology.