The interdependent roles of Ca²⁺ and cAMP in axon guidance

Abstract

Axon guidance is a fundamental process in the developing and regenerating nervous system that is necessary for accurate neuronal wiring and proper brain function. Two of the most important second messengers in axon guidance are Ca(2+) and cAMP. Recently experimental and theoretical studies have uncovered a Ca(2+) - and cAMP-dependent mechanism for switching between attraction and repulsion. Here, we review this process and related Ca(2+) and cAMP interactions, the mechanisms by which necessary intracellular calcium elevations are created, and the pathways, which effect attractive and repulsive responses to the switch.

Calcium signaling in axon guidance

“…A complex pathway which interprets these intracellular Review Trends in Neurosciences August 2014, Vol. 37,No. 8 Ca 2+ signals to determine attraction or repulsion has been described [45,47], together with a recent model which represents this pathway mathematically [42].…”

“…One of the most crucial components of these pathways is calcium [5][6][7][8]. Calcium concentrations in growth cones are regulated both by calcium influx through the plasma membrane and by release from intracellular calcium stores [9,10] (see Glossary).…”

“…Calcium concentrations in growth cones are regulated both by calcium influx through the plasma membrane and by release from intracellular calcium stores [9,10] (see Glossary). A calmodulin-dependent protein kinase II (CaMKII)-calcineurin (CaN) switch often initiates either an attractive (turning towards the highest guidance cue concentration) or repulsive (turning away from the highest guidance cue concentration) response to these intracellular calcium elevations [8]. These responses are effected via the regulation of cytoskeletal components, such as microtubules and actin filaments [11][12][13][14][15], and by membrane dynamics, including vesicle trafficking [16][17][18].…”

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

“…A calmodulin-dependent protein kinase II-calcineurin switch initiates either an attractive or a repulsive response to these intracellular elevations (Sutherland and Goodhill 2015). Th ese responses are mediated via the regulation of cytoskeletal components, such as microtubules and actin fi laments and membrane dynamics, including vesicle traffi cking (Sutherland et al 2014).…”

“…Th ese responses are mediated via the regulation of cytoskeletal components, such as microtubules and actin fi laments and membrane dynamics, including vesicle traffi cking (Sutherland et al 2014).…”