Our thought processes rely on networks of nerve cells called neurons. These networks must be properly formed during development and the neurons must be able to communicate correctly with each other for our brains to function normally. When neurological disorders occur, they can often be traced back to how one or a group of signaling proteins within neurons failed to perform. To understand how these proteins should have worked is not an easy task if one is limited to using traditional biochemical and genetic approaches, because the proteins often carry out different roles at different times and locations inside the cells. One powerful way to identify how the functions of these proteins depends on the location and timing of their activity would be to enable investigators to switch them on or off at precise times or locations inside the cells of intact neural circuits. The current proposal aims to generate a set of tools that can switch proteins on or off in living systems with a pulse of light. Knowledge gained with these tools can lead us one step closer to curing many neurological disorders.

Public Health Relevance

The proposed studies will provide novel imaging tools that empower investigators to directly interrogate and understand the activities of specific signaling proteins at precise times and locations within specific types of neurons in vivo, the outcomes of which can provide mechanistic insights into the pathology and therapeutics of many neurological disorders, and may eventually unravel the molecular basis of intelligence, memory and learning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS071216-03
Application #
8068663
Study Section
Neurotechnology Study Section (NT)
Program Officer
Talley, Edmund M
Project Start
2010-05-15
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
3
Fiscal Year
2011
Total Cost
$188,650
Indirect Cost
Name
University of Connecticut
Department
Genetics
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Borinskaya, Sofya; Velle, Katrina B; Campellone, Kenneth G et al. (2016) Integration of linear and dendritic actin nucleation in Nck-induced actin comets. Mol Biol Cell 27:247-59
Heemskerk, Niels; Schimmel, Lilian; Oort, Chantal et al. (2016) F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. Nat Commun 7:10493
Kedziora, Katarzyna M; Leyton-Puig, Daniela; Argenzio, Elisabetta et al. (2016) Rapid Remodeling of Invadosomes by Gi-coupled Receptors: DISSECTING THE ROLE OF Rho GTPases. J Biol Chem 291:4323-33
Lin, Benjamin; Yin, Taofei; Wu, Yi I et al. (2015) Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration. Nat Commun 6:6619
Ng, K Y; Yin, T; Machida, K et al. (2015) Phosphorylation of Dok1 by Abl family kinases inhibits CrkI transforming activity. Oncogene 34:2650-9
van Unen, Jakobus; Reinhard, Nathalie R; Yin, Taofei et al. (2015) Plasma membrane restricted RhoGEF activity is sufficient for RhoA-mediated actin polymerization. Sci Rep 5:14693
Timmerman, Ilse; Heemskerk, Niels; Kroon, Jeffrey et al. (2015) A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1. J Cell Sci 128:3514
Hayashi-Takagi, Akiko; Yagishita, Sho; Nakamura, Mayumi et al. (2015) Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525:333-8
Das, Sulagna; Yin, Taofei; Yang, Qingfen et al. (2015) Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling. Proc Natl Acad Sci U S A 112:E267-76
Yin, Taofei; Wu, Yi I (2015) Optogenetics: optical control of a photoactivatable Rac in living cells. Methods Mol Biol 1251:277-89

Showing the most recent 10 out of 14 publications