Lars Dreier, Ph.D.

Laboratory Address:
Gonda Center, Room 3309

Mailing Address:
David Geffen School of Medicine at UCLA
Department of Neurobiology
695 Charles E. Young Dr. South
Gonda Center, Room 3309
Los Angeles, CA 90095

Office Address:
Gonda 3506C

Assistant Professor, Neurobiology
Member, Brain Research Institute, Cell & Developmental Biology GPB Home Area
Research Interests
The formation of synapses between neurons and the regulation of signaling through these synapses is fundamental to the function of the nervous system. We are studying mechanisms of synapse formation and regulation of neurotransmitter receptors in the genetic model organism C. elegans using a combination of genetic, cell biological, and biochemical techniques. Analysis of the C. elegans nervous system is relatively easy due to the small number of neurons (302) and the fact that the connectivity between these neurons is known and identical in every animal. To visualize synapses, GFP- or RFP-tagged synaptic proteins can be expressed in subsets of neurons, for example the cholinergic or GABAergic motorneurons, or glutamatergic interneurons.

Recent evidence indicates that regulated degradation of synaptic proteins is an important mechanism to control synapse formation and function. Ubiquitin-dependent degradation is a major pathway for regulated protein degradation. In this pathway, ubiquitin ligases conjugate the small protein ubiquitin to target proteins destined for degradation. We are currently characterizing the function of ubiquitin ligase mutants that affect synapse structure and synaptic transmission at various synapses. The activity of ubiquitin ligases is antagonized by deubiquitinating enzymes that remove ubiquitin from target proteins (in a similar way, protein kinases and phosphatases antagonize each other). Deubiquitinating enzymes are probably as important as ubiquitin ligases in regulating protein degradation, but very few have been characterized to date. The C. elegans genome encodes about 300 ubiquitin ligases and 50 deubiquitinating enzymes. In RNAi based screens, we are now identifying deubiquitinating enzymes that affect synaptic transmission and synapse structure.


Dr. Lars Dreier joined the Department of Neurobiology as an Assistant Professor in 2006. Lars did his Ph.D. work in the Department of Cell Biology, Harvard Medical School, Boston, in the lab of Tom Rapoport, reconstituting the transport of secretory proteins through the Endoplasmic Reticulum (ER) membrane and characterizing the formation of the ER in vitro. In 2000, he joined the lab of Josh Kaplan at the University of California, Berkeley, where he started to work on ubiquitin-dependent regulation of glutamate receptors in C. elegans. Lars moved with the Kaplan lab back to Boston in 2002.


A selected list of publications:

Sun Yu, Vashisht Ajay A, Tchieu Jason, Wohlschlegel James A, Dreier Lars   Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy The Journal of biological chemistry, 2012; 287(48): 40652-60.
Wang, J, G.W. Farr, D.H. Hall, F. Li, K. Furtak, L. Dreier, A.L. Horwich   An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans PLoS Genetics, 2009; 5(1): .
Dreier, L.* Burbea, M.* Kaplan, J. M.   LIN-23-mediated degradation of beta-catenin regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans Neuron, 2005; 46: 51-64.
Burbea, M.* Dreier, L.* Dittman, J. S. Grunwald, M. E. Kaplan, J. M.   Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans Neuron, 2002; 35: 107-20, * contributed equally.
Felbor, U. Dreier, L. Bryant, R. A. Ploegh, H. L. Olsen, B. R. Mothes, W.   Secreted cathepsin L generates endostatin from collagen XVIII Embo J, 2000; 19(6): 1187-94.
Dreier, L. Rapoport, T. A.   In vitro formation of the endoplasmic reticulum occurs independently of microtubules by a controlled fusion reaction J Cell Biol, 2000; 148(5): 883-98.
Panzner, S. Dreier, L. Hartmann, E. Kostka, S. Rapoport, T. A.   Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p Cell, 1995; 81(4): 561-70.