Dr. Worley’s laboratory examines the molecular basis of learning and memory.
In particular, research in the Worley Lab have cloned a set of immediate early genes (IEGs) that are rapidly transcribed in neurons involved in information processing, and that are essential for long-term memory.
IEG proteins can directly modify synapses and provide insight into cellular mechanisms that support synapse-specific plasticity.
For example, Narp is secreted and induces excitatory synapse formation. Homer catalyzes conformational coupling of multi-protein machines involved in calcium signaling. Rheb regulates mTor (target of rapamycin) and protein translation. Arc induces the formation of endosomes that function in trafficking of glutamate receptors.
Thus, rapid de novo transcription provides novel insights into the cellular and neural network basis of behavioral plasticity.
Lab Website: Paul Worley Lab
ES Cell Targeting Core Facility
Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF. “Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation.” Cell. 2011 Oct 28;147(3):615-28.
Hu JH, Yang L, Kammermeier P, Moore CG, Brakeman PR, Tu JC, Yu S, Petralia RS, Li Z, Zhang PW, Park JM, Dong X, Xiao B and Worley PF. “Preso1 dynamically regulates Group1 metabotropic glutamate receptors.” Nature Neuroscience. 2012.
Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M, Kawashima T, Fujii H, Takemoto-Kimura S, Abe M, Natsume R, Chowdhury S, Sakimura K, Worley PF, Bito H. “Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKIIβ.” Cell. 2012 May 11; 149(4):886-98.
Bangash MA, Park JM, Melnikova T, Wang D, Jeon SK, Lee D, Syeda S, Kim J, Kouser M, Schwartz J, Cui Y, Zhao X, Speed HE, Kee SE, Tu JC, Hu JH, Petralia RS, Linden DJ, Powell CM, Savonenko A, Xiao B, Worley PF. Enhanced Polyubiquitination of Shank3 and NMDA receptor in a Mouse Model of Autism. Cell. 2011 May 27;145(5):758-772.
Chang MC, Park JM, Pelkey KA, Grabenstatter HL, Xu D et al. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nat Neurosci. 2010; 13(9):1090-7.