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Abstract
Activation of protein kinase C (PKC) increases microtubule (MT) growth lifetimes, resulting in extension of a nocodazole-sensitive population of MTs in Aplysia growth cones. We examined whether the two phorbol ester-activated PKCs in Aplysia, the Ca(2+)-activated PKC Apl I and the Ca(2+)-independent PKC Apl II, are associated with these MTs. Phorbol esters translocated PKC to the Triton X-100-insoluble fraction, and a significant portion of this translocated pool was sensitive to low concentrations of nocodazole. Low doses of nocodazole had no effect on the amount of PKC in the Triton X-100-insoluble fraction in the absence of phorbol esters, whereas higher doses of nocodazole reduced basal levels of PKC Apl II. The F-actin cytoskeletal disrupter, latrunculin A, removed both PKCs from the Triton X-100-insoluble fraction in both control and phorbol ester-treated nervous systems. PKC Apl II also directly interacted with purified MTs. In detergent-extracted cells, both PKCs immunolocalized predominantly with MTs. PKCs were associated with newly formed MTs invading the actin-rich peripheral growth cone domain after PKC activation. Our results are consistent with a central role for PKCs in regulating MT extension.
Highlights
Kinases are often anchored near their substrates, and this anchoring is often critical for efficient signal transduction (33–35)
The large percentage of PKCs associated with microtubules and actin filaments in neurons suggests that the cytoskeleton is one of the major targets of PKC action in these cells
It will be important to understand how the activity of PKC on microtubules is regulated under physiological conditions to regulate neuronal outgrowth, delivery of materials, and growth cone guidance
Summary
PKC Apl II directly interacted with purified MTs. In detergent-extracted cells, both PKCs immunolocalized predominantly with MTs. PKCs were associated with newly formed MTs invading the actin-rich peripheral growth cone domain after PKC activation. After PKC activation, MTs tend to advance into the P domain because their average MT growth rates increase to exceed retrograde F-actin flow rates (8). PKC Apl II was localized to actin cables in the growth cone (3) Both PKCs translocated to a Triton X-100-insoluble fraction by phorbol esters, and this was initially assumed to represent the actin cytoskeleton (3). Upon activation by phorbol esters, both isoforms of PKC rapidly translocate onto newly assembled MTs, suggesting a direct role for PKC in regulating distal MT advance in neuronal growth cones
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