This seminar is part of the GHUCCTS KL2 Visiting Scholars Seminar Series. Haiyan He, PhD, is an Assistant Professor in Department of Biology at Georgetown University. Dr. He will discuss "A novel nascent protein-degradation-based mechanism for fast homeostatic control of neuronal activity."

ABSTRACT:  Protein synthesis and degradation are both known to be required for brain function and plasticity. Despite the vast number of studies on the involvement of protein synthesis and degradation in the induction and maintenance of synaptic plasticity, our understanding of how neurons achieve the requisite balance of proteostasis remains incomplete. The majority of studies on protein degradation focus on the function of the ubiquitin-mediated proteosome pathway. Here we present evidence for a new mechanism of activity-dependent proteostasis regulation employed by the vertebrate brain that is mediated by a recently discovered neuronal membrane proteasome (NMP). In vitro studies in hippocampal neuronal cultures showed that NMPs degrade nascent proteins in a ubiquitin-independent manner. We investigated the in vivo function of NMPs in the intact brain of Xenopus laevis tadpoles. Combining the bio-orthogonal noncanonical amino acid tagging (BONCAT) method and functional Ca⁺⁺ imaging, as well as behavioral learning paradigm, our data demonstrate a homeostatic function of NMPs in regulating neuronal activity and experience-dependent circuit plasticity. By controlling the accumulation of nascent proteins, NMPs are uniquely positioned to fine tune proteostasis in response to elevated neuronal activity. The NMP-mediated degradation of activity-induced nascent proteins provides a timely regulatory mechanism for the dynamic maintenance of the fine balance needed for proteostasis in neurons, especially in face of fluctuations of neuronal activity, when protein synthesis changes rapidly.

Dr. Haiyan He, Ph.D., completed her PhD at University of Maryland, College Park and had previously conducted her research at Cold Spring Harbor Laboratory and Scripps Research Institute.