In:
Journal of Cell Science, The Company of Biologists, Vol. 119, No. 18 ( 2006-09-15), p. 3799-3810
Abstract:
The unique N-terminal regions of PDE4 cAMP-specific phosphodiesterases confer interaction with distinct signalling and scaffolding proteins. The PDE4A1 isoform is unique in being entirely membrane associated. Its N-terminal region is formed from two helices separated by a mobile hinge, where helix-2 contains a TAPAS1 domain that inserts into the lipid bilayer in a Ca2+-triggered fashion. Here we show that helix-1 is important for intracellular targeting of PDE4A1 in living cells, facilitating membrane association, targeting to the trans-Golgi stack and conferring Ca2+-stimulated intracellular redistribution in a manner that is dependent on the phospholipase-D-mediated generation of phosphatidic acid. The LxDFF motif within helix-1 is pivotal to this, where Leu4-Phe6-Phe7 forms a compact hydrophobic pocket on one side of helix-1 whereas Asp5, located on the opposite face of helix-1, provides the Ca2+-regulation site. Mutation of Asp5 to Ala or the release of Ca2+ from intracellular stores de-restricts trans-Golgi localisation of PDE4A1 allowing it to redistribute in cells in a phosphatidic-acid-dependent manner. This study provides the first evidence for Ca2+-triggered relocalisation of a cAMP phosphodiesterase and indicates a potential means for allowing cross-talk between the cAMP, phospholipase D and Ca2+-signalling pathways.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2006
detail.hit.zdb_id:
1483099-1
SSG:
12
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