Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking.

Migrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in (hTERT)-immortalizedRPE1 (retinal pigment epithelial) cells over long timescales. By live cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed toward protrusions with a 20-min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.

Intracellular organization in cell polarity - placing organelles into the polarity loop.

Many studies have investigated the processes that support polarity establishment and maintenance in cells. On the one hand, polarity complexes at the cell cortex and their downstream signaling pathways have been assigned as major regulators of polarity. On the other hand, intracellular organelles and their polarized trafficking routes have emerged as important components of polarity. In this Review, we argue that rather than trying to identify the prime 'culprit', now it is time to consider all these players as a collective. We highlight that understanding the intimate coordination between the polarized cell cortex and the intracellular compass that is defined by organelle positioning is essential to capture the concept of polarity. After briefly reviewing how polarity emerges from a dynamic maintenance of cellular asymmetries, we highlight how intracellular organelles and their associated trafficking routes provide diverse feedback for dynamic cell polarity maintenance. We argue that the asymmetric organelle compass is an indispensable element of the polarity network.