Transport and local translational regulation of mRNAs in neurons
Chair: Suzanne Zukin
Participants, Gary J. Bassell, Bill Greenough, David G. Wells, Oswald Steward
In the style of "old fashioned" WCBR workshops, where formal presentations are brief
and audience participation in the discussion is encouraged, this session will host a wideranging and speculative WCBR workshop on local protein synthesis in dendrites.
Greenough will discuss recent research on mechanisms whereby the fragile X protein
regulates translation at the synapse via shuttling from polysome translation complexes to
non-translating granules in response to activation of cellular signaling pathways. Wells
will discuss progress on the functional consequences of inhibiting the function of the
mRNA-binding protein CPEB in neurons. He will specifically discuss how inhibiting
this mechanism only in Purkinje neurons produces a loss of the late-phase of cerebellar
LTD and produces ataxic mice. Contrasting the differences between FMRP loss and
CPEB dysfunction in Purkinje neurons will highlight the differences between these two
mechanisms for dendritic mRNA translation. Bassell will discuss the role of FMRP in
activity-dependent mRNA transport and synaptic protein synthesis. He will specifically
discuss trafficking of FMRP in mRNA granules in dendrites and synapses in response to
glutamatergic signaling and the apparent dual role for FMRP in activity-dependent
mRNA transport and synaptic protein synthesis. In cultured neurons from FMR1
knockout mice, the activity-dependent transport of specific mRNAs into dendrites was
impaired. Analysis of glutamate-regulated protein synthesis in synaptoneurosomes
revealed dysregulation of the synthesis of glutamate receptor subunits and associated
proteins. Steward will focus on focus on the apparent rate-limiting nature of the protein
synthetic machinery, and what this implies in terms of translational regulation.
Supplementary Information Please justify inclusion of individuals from the same
institution or who are listed on more than one proposal. Under no circumstances will an
individual be allowed to participate in more than two, non-overlapping sessions.
Bill Greenough is involved in a non-overlapping session on autism wherein he will talk
about parallels between fragile X syndrome and autism, largely in anatomy and sensory
system function. There is no molecular biology of autism to talk about yet, hence no
overlap.