Jerry C. P. Yin
Ph.D University of Wisconsin, Madison
Professor, Departments of Genetics and Psychiatry

Contact Information:
Waisman Center
UW-Madison
1500 Highland Avenue
Madison, WI 53705
E-mail: jcyin@wisc.edu

Research Statement

All animals are capable of learning and remembering associative stimuli. The duration of memory is a function of the strength of training, and different training regimens produce characteristic phases of memory that may each have an independent molecular/cellular basis. Long-term memory, in addition to persisting for the longest time, also requires de novo protein synthesis around the time of training. This program of gene expression raises the critical issue of synaptic specificity--how do neurons only strengthen activated synapses when cell-wide changes in transcription and translation occur?

The Synaptic Tagging hypothesis posits that active synapses, and ones that are co-active within a narrow temporal window, mark themselves upon synaptic activation. This mark or tag allows these synapses to preferentially "capture" and utilize macromolecules synthesized and sent ubiquitously upon activation of gene expression cascades. Capture and utilization contribute to permanent strengthening of synaptic transmission, and is thought to be one of the important mechanisms in memory formation.

We hypothesize that the atypical protein kinase C (aPKC) is a key molecular component of the Tagging complex, recapitulating its roles in marking subcellular location in processes as diverse as asymmetric cell division, cell polarity and oogenesis. In all of these processes, it functions to regulate "localized translation" of repressed mRNAs, affect cytoskeletal architecture, and control the trafficking of protein scaffolds. One of the proteins that the atypical PKC controls is the Fragile X protein, anmRNA binding protein missing in patients with this dysfunction. aPKC somehow is critically involved in the temporally-regulated, localized de-repression of mRNAs bound by Fragile X. We hypothesize that most if not all of the endophenotypes seen in Fragile X result from ectopic, rather than localized, de-repression of translation. We further speculate that many dysfunctions where patients have attention problems may be due to neuronal circuitry defects resulting from aberrant Tagging. Our goal is to identify the molecular players in Tagging, and test their involvement in various dysfunctions.

Representative Publications

Yin, J. C.P., Del Vecchio, M., Zhou, H. and Tully, T. 1995. CREB as a memory modulator: induced expres-
sion of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 81: 107-115.

Drier, E. A., Cowan, M., Tello, M. K., Wu, P., Blace, N., Sacktor, T. C. and Yin, J. C. P. 2002. Memory
formation and enhancement by atypical PKM activity in Drosophila melanogaster. Nat. Neurosci
5: 316-324.

Ruiz-Canada, C., Ashley, J., Moeckel-Cole, S., Drier, E., Yin, J. and Budnik, V. 2004. New synapse formation
is disrupted by misregulation of microtubule stability in aPKC mutants. Neuron 42, 567-80.