Biology subjects

Hernandez-Vega, A.

Publications and source records attributed to Hernandez-Vega, A..

3 recordsLinked to original sources

bioRxiv2018

Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

Tau is an intrinsically disordered protein, which diffuses on microtubules. In neurodegenerative diseases collectively termed tauopathies, tau malfunction and its detachment from axonal microtubules is correlated with microtubule degradation. It is known that tau can protect microtubules from microtubule-degrading enzymes, such as katanin. However, how tau can fulfill such regulative function is still unclear. Using in vitro reconstitution, we here show that tau molecules on microtubules cooperatively form islands of an ordered layer with regulatory qualities distinct from a comparably dense layer of diffusible tau. These islands shield the microtubules from katanin and kinesin-1 but are penetrable by kinesin-8 which causes the islands to disassemble. Our results indicate a new phase of tau, constituting an adjustable protective sheath around microtubules.

biophysics↗

bioRxiv2017

Local Nucleation Of Microtubule Bundles Through Tubulin Concentration Into A Condensed Tau Phase

Non-centrosomal microtubule bundles play important roles in cellular organization and function. Although many diverse proteins are known that can bundle microtubules, biochemical mechanisms by which cells could locally control the nucleation and formation of microtubule bundles are understudied. Here, we demonstrate that concentration of tubulin into a condensed, liquid-like compartment composed of the unstructured neuronal protein tau is sufficient to nucleate microtubule bundles. We show that under conditions of macro-molecular crowding, tau forms liquid drops. Tubulin partitions into these drops, efficiently increasing tubulin concentration and driving the nucleation of microtubules. These growing microtubules form bundles enclosed in a liquid sheath of tau. Our data suggest that condensed compartments of microtubule bundling proteins could promote the local formation of microtubule bundles in neurons by acting as non-centrosomal microtubule nucleation centers, and that liquid-like tau encapsulation could provide both stability and plasticity to long axonal microtubule bundles.

cell biology↗

bioRxiv2016

Rab5-mediated Yolk Endocytosis modulates Zebrafish Epiboly Biomechanics and Tissue Movements

Morphogenetic processes demand the coordinated allocation of cells and tissues to their final destination in a spatio-temporal controlled way. Identifying how these morphogenetic movements are directed and implemented is essential for understanding morphogenesis. Topographical and scalar differences in adhesion and contractility within and between cells are essential, yet, the role that membrane remodeling may play remains less clear. To clarify how surface turnover and dynamics may modulate tissue arrangements we studied epiboly in the zebrafish. During epiboly the blastoderm expands as a result of an asymmetry of mechanical tension along the embryo surface. In this scenario, we found that the membrane removal by macropinocytosis of the external yolk cell syncytial layer (E-YSL) ahead of the blastoderm is key for epiboly progression In early zebrafish embryos, the activity of the GTPase Rab5ab was essential for endocytosis, and interference in its expression exclusively in the yolk cell resulted in the reduction of yolk cell actomyosin contractility, the disruption of cortical and internal yolk flows, a disequilibrium in force balance and as a result epiboly impairment. We conclude that regulated membrane remodeling is crucial for directing cell and tissue mechanics and coordinating morphogenetic movements during epiboly.

developmental biology↗