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Phosphatidylinositol kinase enzymes regulate the retrograde axonal transport of NT‐3 and NT‐4 in sympathetic and sensory neurons
Author(s) -
Bartlett Selena E.,
Reynolds Anna J.,
Weible Michael,
Hendry Ian A.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10201
Subject(s) - wortmannin , axoplasmic transport , retrograde signaling , neurotrophin , biology , microbiology and biotechnology , kinase , ly294002 , phosphatidylinositol , signal transduction , neuroscience , receptor , biochemistry
Phosphatidylinositol 3‐kinase (PI3‐kinase) and phosphatidylinositol 4‐kinase (PI4‐kinase) enzymes are an important family of signaling molecules that have been implicated in the regulation of intracellular vesicle trafficking. It has previously been shown that PI3‐kinase and PI4‐kinase enzymes regulate neuronal survival and the retrograde axonal transport of nerve growth factor in sympathetic and sensory neurons. We have extended these studies to examine the role these enzymes play in the regulation of the retrograde axonal transport of neurotrophin‐3 (NT‐3) and neurotrophin‐4 (NT‐4) in sympathetic and sensory neurons in vivo. Wortmannin (0.1 nmol/eye), a PI3‐kinase and PI4‐kinase antagonist, reduced the amount of 125 I‐NT‐3 retrograde transport in sympathetic neurons by approximately 50% and 125 I‐NT‐4 in sympathetic neurons by approximately 40% and sensory neurons by approximately 20%. The PI3‐kinase antagonist LY294002 (100 nmol/eye) reduced the retrograde axonal transport of 125 I‐NT‐4 in sympathetic and sensory neurons, and 125 I‐NT‐3 in sympathetic neurons. Phenylarsine oxide (PAO), a PI4‐kinase antagonist, significantly inhibited 125 I‐NT‐4 retrograde axonal transport in sympathetic and sensory neurons. These results show that wortmannin‐sensitive PI3‐kinases and PI4‐kinases may be involved in NT‐3 and NT‐4 retrograde axonal transport. The retrograde axonal transport of neurotrophic factors in sympathetic and sensory neurons in vivo appears to depend upon the activation of different receptors and second messenger cascades at the nerve terminal. © 2002 Wiley‐Liss, Inc.