Biology subjects

Bilodeau, P.

Publications and source records attributed to Bilodeau, P..

3 recordsLinked to original sources

bioRxiv2020

Activation of Rab11a and endocytosis by Phosphatidylinositol 4-kinase III beta promotes oncogenic signaling in breast cancer

Endosomes are now recognized as important sites for regulating signal transduction. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII{beta}) regulates both endocytic kinetics and receptor signaling in breast cancer cells. PI4KIII{beta} generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of breast cancers. However, the molecular mechanism by which PI4KIII{beta} promotes breast cancer is unclear. We demonstrate that ectopic PI4KIII{beta} expression increases the rates of both endocytic internalization and recycling. PI4KIII{beta} deletion reduces endocytic kinetics accompanied by a concomitant decrease in activity of the Rab11a GTPase, a protein required for endocytic function. Finally, we find that PI4KIII{beta} activates IGF-IR{beta} signaling dependent on endosome function. Regulation of endocytic function by PI4KIII{beta} is independent of its kinase activity but requires interaction with the Rab11a. This suggests that PI4KIII{beta} controls endosomal kinetics and signaling by directly modulating Rab11a function. Our work suggests a novel regulatory role for PI4KIII{beta} in endosome function and plasma membrane receptor signaling.

cancer biology↗

bioRxiv2019

Mitochondria tether to Focal Adhesions during cell migration and regulate their size.

Mitochondria are the key generators of ATP in a cell. Visually, they are highly dynamic organelles that undergo cellular fission and fusion events in response to changing cellular energy requirements. Mitochondria are now emerging as regulators of mammalian cell motility. Here we show that mitochondria infiltrate the leading edge of NIH3T3 fibroblasts during migration. At the leading edge, we find that mitochondria move to and tether to Focal Adhesions (FA). FA regulate cell migration by coupling the cytoskeleton to the Extracellular Matrix through integrin receptors. Importantly, we find that inhibition of mitochondrial ATP generation concomitantly inhibits FA size. This suggests that mitochondrial energy production regulates migration through FA control.

cell biology↗

bioRxiv2019

Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and focal adhesion number.

Cell shape is regulated by cell adhesion and cytoskeletal and membrane dynamics. Cell shape, adhesion and motility have a complex relationship and understanding them is important in understanding developmental patterning and embryogenesis. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII{beta}) regulates cell shape, migration and Focal Adhesion (FA) number. PI4KIII{beta} generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of human breast cancers. PI4KIII{beta} and the PI4P it generates regulate a variety of cellular functions, ranging from control of Golgi structure, fly fertility and Akt signaling. Here, we show that loss of PI4KIII{beta} expression decreases cell migration and alters cell shape in NIH3T3 fibroblasts. The changes are accompanied by an increase in the number of FA in cells lacking PI4KIII{beta}. Furthermore, we find that PI4P-containing vesicles move to the migratory leading-edge during migration and that some of these vesicles tether to and fuse with FA. Fusion is associated with FA disassembly. This suggests a novel regulatory role for PI4KIII{beta} and PI4P in cell adhesion and cell shape maintenance.

cell biology↗