PT  - JOURNAL ARTICLE
AU  - Erik S Linklater
AU  - Emily D Duncan
AU  - Ke-Jun Han
AU  - Algirdas Kaupinis
AU  - Mindaugas Valius
AU  - Traci R Lyons
AU  - Rytis Prekeris
TI  - Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion
AID  - 10.1101/2021.04.01.438077
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.01.438077
4099  - http://biorxiv.org/content/early/2021/04/01/2021.04.01.438077.short
4100  - http://biorxiv.org/content/early/2021/04/01/2021.04.01.438077.full
AB  - Rab40b is a SOCS box containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b/Cullin5 binding decreases cell motility and invasive potential, and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b/Cullin5 dependent localized ubiquitylation and degradation. Thus, we propose a model where the Rab40b/Cullin5 dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.Competing Interest StatementThe authors have declared no competing interest.