Kang Shen, PhD
Department of Biology
Howard Hughes Medical Institute Stanford University
(November 5, 2014)
Molecular Mechanisms of Dendrite Morphogenesis in C. Elegans
Neuronal circuits and networks are formed when neurons form synaptic connections: a point of communication from one neuron to another. The synapse is this point, the spot where the signals from one neuron reaches the dendrite of the next. The growth and branching of dendrites, like the branches of a tree, affect how connections and networks eventually form. Dr. Shen has identified a receptor, DMA-1, that helps to regulate the growth and branching of dendrites. Too much or too little DMA-1 can halt dendritic growth or alter development, eventually affecting the formation of networks of neurons.
Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes.
In a kpc-1 mutant, the level of DMA- 1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis.