Cellular and Molecular Neurobiology
Author: María Pilar Canal | Email: pili.canal31@gmail.com
María Pilar Canal1°, Fernando Diego Marengo1°2°,Luciana Inés Gallo1°2°
1° IFIBYNE (CONICET-UBA)
2° FBMC – FCEN – UBA
Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by an expanded poly-glutamine stretch in the Huntingtin protein (Htt). HD animal models show decreased dense-core vesicle (DCV) secretion, and HD patients feature symptoms associated with altered neuropeptide functions. Moreover, Htt regulates Rab11a, a novel protein that we described regulating DCV secretion. However, Htt biological functions and the basic mechanisms by which mutated Htt (mHtt) affects the regulated-secretory pathway, including the possible interactions between mHtt and Rab11a, in neuronal and neuroendocrine cells, remain unclear.
In alignment with emerging evidence suggesting a role of Htt in vesicle trafficking, we analyzed DCV distribution and mobility in chromaffin cells using confocal imaging and bioimage analysis tools. We report that mHtt overexpression decreased DCV presence at the cell periphery and modified DCV transport regimes, showing a predominance of confined motion, with respect to control cells. When both mHtt and Rab11aWT were coexpressed, a partial reversion of these effects was found. In particular, during stimulation we observed a shift towards a higher DCV presence at the cell periphery, and an increased motility of DCV that resembles that of control cells. This data contributes to our understanding of mHtt effects in neurosecretory cells, and by elucidating DCV trafficking regulation, we expect to find potential targets to revert them.