Lakshmi Sundararajan

Lakshmi Sundararajan

Postdoctoral Fellow, Cell and Developmental Biology

Hometown: Madurai, Tamil Nadu, India

 

Education:

B.Tech. Biotechnology

Anna University

Sivakasi, Tamil Nadu

 

​Ph.D. in Molecular, Cell and Developmental Biology

University of Kansas

Lawrence, Kansas

 

 

 

 

 

Research Description

Actin polymerization plays an important role in cell migration and axon/dendrite outgrowth. Both attractive and repulsive signals regulate actin-mediated protrusions. Here we show that actin plays a key role in the process of dendritic self-avoidance Dendrites arising from a single neuron rarely overlap due to contact-dependent retraction. We have observed this phenomenon in the highly branched C. elegans nociceptive neuron, PVD, in which the tertiary sister dendrites retract upon mutual contact. We have previously shown that PVD self-avoidance is mediated by the short-range diffusible cue, UNC-6/Netrin, and its receptors, UNC-40/DCC and UNC-5 (Smith CJ, et al., 2012).  A genetic survey of candidate UNC-6 downstream components established that the actin polymerizing protein, UNC-34/Ena/VASP is also required for PVD self-avoidance. We used ‘pseudo-TIRF’ microscopy (with Matt Tyska)  to detect a burst of F-actin accumulation at the tips of retracting PVD dendrites immediately after contact. We also observed that UNC-34/Ena co-localizes with F-actin during this process (Cody Smith). These findings suggest the paradoxical idea that UNC-34-mediated growth of nascent actin filaments is required for dendrite retraction. This model may be explained by the observation that the non-muscle myosin, NMY-1, is necessary for PVD dendrite retraction and could mediate this effect by retrograde flow. Genetic studies are consistent with the proposal that NMY-1 functions in the same pathway as UNC-34. Together, these data suggest that UNC-6/Netrin signaling triggers the local assembly of new actin filaments, which then engage NMY-1 to elicit dendrite retraction. My ongoing experiments are designed to confirm that NMY-1 function is cell-autonomous and to visualize NMY-1 localization in tertiary dendrites during the self-avoidance response. 

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