Microtubule-Associated Type II Protein Kinase A Is Important for Neurite Elongation
نویسندگان
چکیده
Neuritogenesis is a process through which neurons generate their widespread axon and dendrites. The microtubule cytoskeleton plays crucial roles throughout neuritogenesis. Our previous study indicated that the amount of type II protein kinase A (PKA) on microtubules significantly increased upon neuronal differentiation and neuritogenesis. While the overall pool of PKA has been shown to participate in various neuronal processes, the function of microtubule-associated PKA during neuritogenesis remains largely unknown. First, we showed that PKA localized to microtubule-based region in different neurons. Since PKA is essential for various cellular functions, globally inhibiting PKA activity will causes a wide variety of phenotypes in neurons. To examine the function of microtubule-associated PKA without changing the total PKA level, we utilized the neuron-specific PKA anchoring protein MAP2. Overexpressing the dominant negative MAP2 construct that binds to type II PKA but cannot bind to the microtubule cytoskeleton in dissociated hippocampal neurons removed PKA from microtubules and resulted in compromised neurite elongation. In addition, we demonstrated that the association of PKA with microtubules can also enhance cell protrusion using the non-neuronal P19 cells. Overexpressing a MAP2 deletion construct which does not target PKA to the microtubule cytoskeleton caused non-neuronal cells to generate shorter cell protrusions than control cells overexpressing wild-type MAP2 that anchors PKA to microtubules. Finally, we demonstrated that the ability of microtubule-associated PKA to promote protrusion elongation was independent of MAP2 phosphorylation. This suggests other proteins in close proximity to the microtubule cytoskeleton are involved in this process.
منابع مشابه
Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation
Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where...
متن کاملThe inositol polyphosphate 5-phosphatase, PIPP, Is a novel regulator of phosphoinositide 3-kinase-dependent neurite elongation.
The spatial activation of phosphoinositide 3-kinase (PI3-kinase) signaling at the axon growth cone generates phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3), which localizes and facilitates Akt activation and stimulates GSK-3beta inactivation, promoting microtubule polymerization and axon elongation. However, the molecular mechanisms that govern the spatial down-regulation of PtdIns(...
متن کاملModulation of H2O2- Induced Neurite Outgrowth Impairment and Apoptosis in PC12 Cells by a 1,2,4-Triazine Derivative
Introduction: Increased oxidative stress is widely accepted to be a factor in the development and progression of Alzheimer’s disease. Triazine derivatives possess a wide range of pharmacological activities including anti-oxidative and anti-in.ammatory actions. In this study, we aimed to investigate the possible protective effect of 3-thioethyl-5,6-dimethoxyphenyl-1,2,4-triazine (TEDMT) on H2O2-...
متن کاملSense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability.
Microtubules are fundamental elements participating in many aspects of cell behavior and maintenance, yet the factors regulating microtubule behavior in vivo remain poorly understood. Employing the nerve growth factor (NGF)-responsive cell line, PC12, we have used sense and antisense DNA transfection strategies to examine the role of the microtubule-associated protein (MAP) tau in several aspec...
متن کاملRapid microtubule-dependent induction of neurite-like extensions in NIH 3T3 fibroblasts by inhibition of ROCK and Cbl.
A number of key cellular functions, such as morphological differentiation and cell motility, are closely associated with changes in cytoskeletal dynamics. Many of the principal signaling components involved in actin cytoskeletal dynamics have been identified, and these have been shown to be critically involved in cell motility. In contrast, signaling to microtubules remains relatively uncharact...
متن کامل