Dendritic spines are micron-sized structures on dendrites that contain the majority of excitatory synapses in the brain. Synapses mediate neuronal communication, and they undergo activity- dependent modifications during development as well as during learning and memory. Defects in the morphology of dendrite spine morphology are correlated with synaptic impairment. Consequently, these defects are associated with numerous cognitive and degenerative disorders, including intellectual disability, schizophrenia, and Alzheimer's disease. Dynamic remodeling of the actin cytoskeleton is the primary driver of spine development and activity- dependent modifications. However, our understanding of the actin mechanisms underlying spine structure and dynamics remain largely limited. My overall goal is to determine the function of the small actin-binding protein, LIM and SH3 domain protein 1 (LASP1), in dendritic spine development and synaptic plasticity. To that end, I will use high resolution live-cell imaging approaches and electrophysiology in combination with genetic and pharmacological methods to examine LASP1 function. My investigation includes the following two general aims: 1) determine the role of LASP1 in synaptic plasticity and activity-dependent spine morphogenesis; and 2) examine the molecular mechanisms regulating LASP1 function in spines. This study will lead to a greater understanding of the molecular underpinnings of dendritic spine development, with important implications for our knowledge of learning and memory. In addition, because spine dysfunction is a common feature of many neurological disorders, investigating LASP1 function in spines may lead to a greater understanding of their underlying pathophysiology.
Dendritic spines are small highly plastic structures on neurons that are important for learning and memory. This project will investigate the role of an actin cytoskeleton-binding cell signaling protein named LASP1 in the development of dendritic spines and synaptic plasticity. A better understanding of the fundamental cellular and molecular mechanisms underlying dendritic spine morphogenesis and synaptic plasticity is essential for the development of therapies for the numerous cognitive and neurodegenerative disorders associated with defects in dendritic spine dysfunction.
|Lei, Wenliang; Myers, Kenneth R; Rui, Yanfang et al. (2017) Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity. J Cell Biol 216:2551-2564|
|Lei, Wenliang; Omotade, Omotola F; Myers, Kenneth R et al. (2016) Actin cytoskeleton in dendritic spine development and plasticity. Curr Opin Neurobiol 39:86-92|
|Myers, Kenneth R; Liu, Guanglu; Feng, Yue et al. (2016) Oligodendroglial defects during quakingviable cerebellar development. Dev Neurobiol 76:972-82|