Biology subjects

Jimenez, A. J.

Publications and source records attributed to Jimenez, A. J..

3 recordsLinked to original sources

bioRxiv2023

Phase partitioning initiates Rab protein membrane domain formation and promote vesicle tethering

Diverse cellular processes are regulated by the formation of specific membrane domains displaying specific lipid and protein compositions. Liquid-liquid phase separation (LLPS) recently emerged as one possible mechanism for their biogenesis, but the examples remain scarce and the impact of LLPS properties on this process is not well established. Rab GTPases are present on all intracellular membranes and play a crucial role in membrane identity, trafficking and compartmentalization. Domain formation is thought to play a central role in Rab functions. Here we show that several Rab partners with common structural characteristics present LLPS properties, some being able to co-condensate or on the contrary presenting immiscible properties. These properties limit the recruitment of Rabs to the membrane sub-domains defined by the condensates of their specific partners. We further show that those LLPS properties control the recruitment of Rab5 to Rabaptin5 condensates ensuring Rab5 functions in regulating endocytic vesicle tethering and fusion. We propose a universal mechanism for Rab domain formation, delimitation, growth and docking based on LLPS properties of Rab partners.

cell biology↗

bioRxiv2023

A phosphorylation switch regulates RAB6 function during mitosis

RAB GTPases are key regulators of membrane trafficking in eukaryotic cells. In addition to their role in interphase, several RAB proteins, including Golgi-associated RAB6, have mitotic functions. The aim of this study was to investigate how the interphasic and mitotic functions of RAB6 could be regulated. Since phosphorylation is a key regulatory process in mitosis, we looked for specific mitotic phosphorylation of RAB6 using a phospho-proteomic approach. We found that RAB6 is phosphorylated at position S52 by the mitotic kinase Pololike kinase 1 (Plk1) in mitosis. Phosphorylated RAB6 localizes at the spindle poles from prophase to anaphase. In metaphase, we observed RAB6A-positive structures containing Mad1 and Mad2 moving along the mitotic spindle via the dynein-dynactin complex. We provide evidence that phosphorylation impairs RAB6A binding to some of its known partners, including p150Glued and Bicaudal-D2. In addition, the overexpression of RAB6A phospho-mutants lead to mitosis and cytokinesis defects. Our results suggest that a cycle of RAB6 phosphorylation/dephosphorylation is required for cell division.

cell biology↗

bioRxiv2020

Acto-myosin network geometry defines centrosome position

The centrosome is the main organizer of microtubules and as such, its position is a key determinant of polarized cell functions. As the name says, the default position of the centrosome is considered to be the cell geometrical center. However, the mechanism regulating centrosome positioning is still unclear and often confused with the mechanism regulating the position of the nucleus to which it is linked. Here we used enucleated cells plated on adhesive micropatterns to impose regular and precise geometrical conditions to centrosome-microtubule networks. Although frequently observed there, the equilibrium position of the centrosome is not systematically at the cell geometrical center and can be close to cell edge. Centrosome positioning appears to respond accurately to the architecture and anisotropy of the actin network, which constitutes, rather than cell shape, the actual spatial boundary conditions the microtubule network is sensitive to. We found that the contraction of the actin network defines a peripheral margin, in which microtubules appeared bent by compressive forces. The disassembly of the actin network away from the cell edges defines an inner zone where actin bundles were absent and microtubules were more radially organized. The production of dynein-based forces on microtubules places the centrosome at the center of this inner zone. Cell adhesion pattern and contractile forces define the shape and position of the inner zone in which the centrosome-microtubule network is centered.

cell biology↗