Switching Tracks with cAMP

Abstract

The intracellular transport of organelles takes place along both microtubules (MTs) and actin filaments (AFs). Kinesin and dynein "molecular motors" drive transport in opposing directions along MTs, which subserve long-distance transport, whereas myosins drive transport along AFs, which are involved in local movements. The mechanisms regulating organelle transfer between these two cytoskeletal systems, however, remain unclear. Rodionov et al. studied adrenalin-dependent redistribution of membrane-bounded pigment granules in cultured fish melanophores to investigate the alternative hypotheses that organelle switching between these two elements of the cytoskeleton depended on regulation of the relative density of MTs and AFs or on second messenger-dependent regulation of the molecular motors. The authors tracked the movement of individual pigment granules along MTs in both directions and, after MT disruption, along AFs. Granule movement along MTs was independent of MT density (assessed in different regions of the cell) or pharmacologically produced decreases in AF density. The authors combined immunostaining for adenosine 3',5'-monophosphate (cAMP) (by fixing melanophores with acrolein and using antibodies against a cAMP-acrolein complex) with pharmacological manipulation to show that changes in cAMP concentration and in protein kinase A activity independently affected movement on AFs and in both directions along MTs. Moreover, pigment granule switching from MTs to AFs during granule dispersion (associated with adrenaline withdrawal) depended on a reduction in intracellular cAMP that took place after the onset of dispersion. Thus pigment granule movement and switching between the two cytoskeletal systems appear to be regulated by changes in the concentration of cAMP, which in turn regulates activity of the molecular motors, and not through the concentrations of cytoskeletal elements. V. Rodionov, J. Yi, A. Kashina, A. Oladipo, S. P. Gross, Switching between microtubule- and actin-based transport systems in melanophores is controlled by cAMP levels. Curr. Biol. 13 , 1837-1847 (2003). [Online Journal]