Unconventional Roles of Dynein Light Chains
Unconventional Roles of Dynein Light Chain in Axonal Outgrowth, Neurogenesis, and Cell Division
Coordinated changes in microtubules and microfilaments are known to be essential for the morphological development of neurons. However, little is known about the underlying molecular machinery linking the crosstalk between these two cytoskeletal systems in developing neurons. In collaboration with Dr. Alfredo C‡ceres (INIMEC-CONICET, link http://www.immf.uncor.edu/), our lab recently found that the dynein light chain Tctex-1 acts as a regulatory link between the actin and microtubule cytoskeletons and participates in multiple aspects of hippocampal neuron development, including initial neurite sprouting, establishment of axon polarity, and dendrite arborization.
Tctex-1 was initially discovered as a light chain subunit of dynein complex and has a well-characterized role as a cargo adaptor for microtubule-based transport. Using cultured hippocampal neurons as a model system, our recent data suggest that the selectively high level of endogenous Tctex-1 at the growth cone of growing axons drives fast neurite extension by modulating actin dynamics and Rac1 activity. Further evidence has suggested that the neuritic and axogenic effect exerted by Tctex-1 is independent from its cargo adaptor role in dynein motor transport. These findings provide a strong argument that this dynein subunit may have another role outside the dynein complex. Finally, phosphorylation at the Thr94 residue seems to act as a switch between Tctex-1's role as a motor cargo adaptor in the microtubule transport system and its role as a microfilament modulator. The lab is currently exploring the molecular details of the signaling pathway controlling Tctex-1's function as a switch in neuronal polarization.
The dual function of Tctex-1 as a motor cargo adaptor in the microtubule transport system and as a microfilament modulator may also mean that it plays an important part in other cellular events (e.g., cell division, cell migration) that require a coordinated collaboration between the two cytoskeleton systems. We are interested in investigating these roles of Tctex-1 in the context of neurogenesis because our recent data showed that Tctex-1 is highly enriched in mitotic progenitors at the germinal zones of the adult brain. A combinatory use of in vivo (e.g., genetically engineered mice, in utero electroporation) and in vitro approaches are being employed to study these questions.
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