Journal Article

Spatial and temporal second messenger codes for growth cone turning

Nicol, Xavier, Spitzer, Nicholas C, Hong, Kwan Pyo

2011

Overview

Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1–dependent axon guidance. In filopodia, Netrin-1–dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: adenosine monophosphate / Animals / Axons / Biological Sciences / Calcium / Calcium - metabolism / Cell growth / Cells, Cultured / Colorectal cancer / Colorectal carcinoma / colorectal neoplasms / cyclic AMP / Cyclic AMP - metabolism / Growth cones / Growth Cones - metabolism / Nerve Growth Factors - physiology / Netrin Receptors / Netrin-1 / Neurons / Neurons - cytology / Neuroscience / Proteins / Pseudopodia / Receptors / Receptors, Cell Surface - physiology / Second Messenger Systems - physiology / second messengers / Signal transduction / Spinal cord / Trajectories / Tumor Suppressor Proteins - physiology / Vehicles / Xenopus - embryology