Calcium gradients underlying cell migration

doi:10.1016/j.ceb.2011.12.002

Current Opinion in Cell Biology

Volume 24, Issue 2, April 2012, Pages 254-261

https://doi.org/10.1016/j.ceb.2011.12.002 Get rights and content

The calcium ion is the simplest and most versatile second messenger in biology. Harboring a myriad of calcium effector proteins, migrating cells display an exquisite multiscaled and multilayered architecture of intracellular calcium dynamics. In motile fibroblasts, for instance, there are transient calcium microdomains (‘calcium flickers’) of ∼5 μm in diameter and 10–2000 ms in duration, a rising flicker activity gradient along the rear-to-front axis, and a shallow background calcium concentration gradient in the opposite direction. When subjected to external gradients of guidance cues, local flicker gradients are created de novo in the leading edge, which steer cells to turn in new directions as defined by the asymmetry of the flicker activity, apparently by a stochastic decision-making mechanism. These recent findings provide a glimpse into how spatiotemporally coordinated calcium gradients orchestrate cellular behavior as complex as directional movement.

Introduction

Cell migration is fundamental to embryogenesis, immune surveillance, and wound healing, as well as the development of atherosclerosis and the metastasis of tumors. Conceptually, it involves three interdependent yet separable components: the formation and maintenance of cell polarity, activation of motility machinery for linear locomotion, and turning or changing direction of movement in response to gradients of environmental cues. Though calcium signaling has long been known to play important roles in regulating cell migration ([1, 2, 3••], see also [4•, 5•, 6•] for recent reviews), we are just beginning to appreciate how distinctive calcium gradients, their exquisite spatiotemporal coordination, and their interplay and integration with other migratory signals, impact on multiple facets of cell migration.

Section snippets

Spatiotemporal calcium dynamics in migrating cells

In all cells, a 10,000-fold gradient of free calcium concentration ([Ca²⁺]) exists across the plasma membrane; a similar gradient is found between the compartments of the endoplasmic reticulum (ER) and the cytosol. Many cytosolic calcium signaling cascades are initiated by rapid mobilization of calcium ions down their electrochemical gradients across the plasmalemmal and ER membranes, the primal source from which all intracellular calcium dynamics and gradients emerge [7]. Calcium entry from

Decoding calcium gradients by effector proteins

Decoding intracellular calcium gradients is orchestrated by a myriad of calcium effector proteins (Table 1). Before delving into details, we discuss a few critical determinants that govern local calcium signaling. Location: Effector proteins within calcium microdomains created by open calcium channels have preferential access to high local calcium signals and can thus be activated in spite of low ambient calcium. Kinetics: Differences in calcium association and dissociation kinetics dictate

Steering turning by stochastic calcium microdomains

Directional movement critically hinges on the ability of a cell to turn toward a particular pathway in response to guidance cues. The leading lamella serves as the center for cue-sensing, decision-making, and execution of turning (at least the first steps of this compound process). Recent studies shed light on the calcium flicker as the central player, and reveal the beautiful cellular logic in steering fibroblasts in two-dimensional migration and chemotaxis. Salient features of the calcium

Perspective

Recent studies have unveiled the amazingly rich spatiotemporal architecture of calcium dynamics and novel signaling mechanisms in migrating cells. However, we are only at the beginning of deciphering how distinctive calcium gradients impact on a multitude of effector proteins to orchestrate cellular behavior as complex as directional movement. The flicker model for calcium steering of cell migration provides a glimpse of the beauty and complexity of the drama unfolding in the leading edge of a

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

This work was supported by the National Basic Research Program of China (2011CB809102) and the National Science Foundation of China (31130067 and 30900264).

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View full text

Calcium gradients underlying cell migration

Introduction

Section snippets

Spatiotemporal calcium dynamics in migrating cells

Decoding calcium gradients by effector proteins

Steering turning by stochastic calcium microdomains

Perspective

References and recommended reading

Acknowledgements

Physiol Rev

Science

Am J Physiol Heart Circ Physiol

Science

J Cell Biochem

Trends Cell Biol

Physiol Rev

Nat Methods

Exp Mol Med

FEBS Lett

J Biol Chem

Biochemistry

Biochem Biophys Res Commun

Nature

J Biol Chem

Cytosolic free calcium and the cytoskeleton in the control of leukocyte chemotaxis

Physiol Rev

Cell migration: integrating signals from front to back

Science

Calcium gradients underlying polarization and chemotaxis of eosinophils

Science

Calcium in tumour metastasis: new roles for known actors

Nat Rev Cancer

Cross-talk between calcium and protein kinase A in the regulation of cell migration

Curr Opin Cell Biol

The molecular basis for calcium-dependent axon pathfinding

Nat Rev Neurosci

Ca2+ influx through L-type Ca2+ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration

J Biol Chem

Transient receptor potential cation channels in disease

Physiol Rev

Calcium signalling: dynamics, homeostasis and remodelling

Nat Rev Mol Cell Biol

STIM1, an essential and conserved component of store-operated Ca2+ channel function

J Cell Biol

Calcium flickers steer cell migration

Nature

Calcium signalling during chemotaxis

Ciba Found Symp

A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration

Cell Calcium

HGF/SF and menthol increase human glioblastoma cell calcium and migration

Biochem Biophys Res Commun

Ca²⁺ influx through L-type Ca²⁺ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration

STIM1, an essential and conserved component of store-operated Ca²⁺ channel function