![]() ![]() An essential role for katanin in severing microtubules in the neuron. Microtubule nucleation and release from the neuronal centrosomes. Microtubule formation and neurite outgrowth in cerebellar macroneurons that develop in vitro: evidence for the involvement of the microtubule-associated proteins MAP1a, HMW-MAP2 and tau. Nerve growth factor induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors. Fine structural changes in neurons associated with colchicine inhibition of nerve fiber formation in vitro. Axon growth: role of microfilaments and microtubules. Ultrastructure and function of growth cones and axons of cultured nerve cells. Microtubule-induced cortical cell polarity. Cortical control of microtubule stability and polarization. Evolutionary conservation of microtubule-capture mechanisms. Force generation by microtubule assembly/disassembly in mitosis and related movements. Beyond self-assembly: from microtubules to morphogenesis. Structural insights into microtubule function. The role of the cytoskeleton during neuronal polarization. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. An excellent short review that shifted attention to microtubules as key regulators of neuronal polarization.ĭent, E. Neuronal polarity: microtubules strike back. Polarity proteins in axon specification and synaptogenesis. The role of Rho GTPases in neuronal development. Breaking the neuronal sphere: regulation of the actin cytoskeleton in neuritogenesis. New insights into the molecular mechanisms specifying neuronal polarity in vivo. Neuronal polarity: from extracellular signals to intracellular mechanisms. IGF-1 receptor is essential for the establishment of hippocampal neuronal polarity. Recently, dynamic microtubules have been implicated in spine development.Ĭraig, A. Microtubules have also been implicated in regulating the conversion of a motile growth cone into a synaptic terminal. Positive and negative feedback loops mediated by small Rho GTPases, guanine nucleotide exchange factors, GTPase activating proteins and their downstream effectors also regulate the crosstalk between microtubules and actin filaments that is required for axon and dendrite formation.ĭifferences in the orientation of microtubules distinguish axons from dendrites, and the minus end-based motor dynein has a crucial role in organizing dendritic arbors and the uniform orientation of axonal microtubules. ![]() Plus end tracking proteins associate and specifically accumulate at the plus ends of microtubules, and control microtubule dynamics, growth directionality and interactions with components of the cell cortex. The plus ends of microtubules have a central role in the interactions that occur between microtubules and the actin cytoskeleton, which are required for neuronal polarization. Some of them interact with components of the cell cortex to activate signalling pathways required for regulating actin dynamics and axonal growth. Stable microtubules provide nucleation seeds for microtubule assembly and protrusion, as well as tracks for the preferential binding of microtubule-based motors that transport membrane-bound organelles and regulatory macromolecular complexes during axon formation.ĭynamic microtubules in growth cones act as sensors of cellular conditions by extending in various directions in the peripheral actin-rich domain. Neuronal microtubules are regulated by many proteins, including assembly promoting factors, such as collapsin response mediator protein 2 (CRMP2) stabilizers, such as structural or classical microtubule-associated proteins (MAPs) destabilizing factors, such as stathmin microtubule severing proteins, such as katanin plus end tracking proteins, such as adenomatous polyposis coli and end-binding protein 1 (also known as MAPRE1) microtubule-based motors of the kinesin and dynein superfamilies and multiple kinases, such as glycogen synthase kinase 3, LKB1 (also known as STK11) and LKB1's interacting partner STRAD. Phosphoinositide 3-kinase (PI3K) signalling, local actin instability in growth cones and the selective stabilization of microtubules in a particular neurite have emerged as crucial events triggering axon specification. One of the key questions of neurobiology is how neurons polarize to acquire two molecularly and functionally distinct compartments that emerge from the cell body: a single axon and multiple dendrites, which provide the basis for unidirectional signal transmission in the mature nervous system.Ĭultures of hippocampal pyramidal neurons have been used as a model system to analyse the cellular and molecular mechanisms that underlie the development and maintenance of neuronal polarity. ![]()
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