No abstract

No abstract

No abstract

Tubulin cofactors, initially identified as a-, b-tubulin folding proteins, are now believed to participate in the complex tubulin biogenesis and degradation routes, and thus to contribute to microtubule functional diversity and dynamics. However, a concrete role of tubulin cofactor B (TBCB) remains to be elucidated because this protein is not required for tubulin biogenesis, and it is apparently not essential for life in any of the organisms studied. In agreement with these data, here we show that TBCB localizes at the transition zone of the growth cones of growing neurites during neurogenesis where it plays a role in microtubule dynamics and plasticity. Gene silencing by means of small interfering RNA segments revealed that TBCB knockdown enhances axonal growth. In contrast, excess TBCB, a feature of giant axonal neuropathy, leads to microtubule depolymerization, growth cone retraction, and axonal damage followed by neuronal degeneration. These results provide an important insight into the understanding of the controlling mechanisms of growth cone microtubule dynamics. Keywords: axonal growth control, giant axonal neuropathy, microtubule dynamics, neurogenesis, tubulin cofactor B. The establishment of connections between neurons and their targets is of fundamental importance to the genesis of a functional nervous system. A goal of modern developmental neuroscience and cell biology is to understand how axons are extended and how this process is controlled. However, despite the great deal of progress that has been made in understanding the nature of the extracellular signals that induce axon growth, we still know relatively little about the intracellular molecular mechanisms that elicit neurite extension.A role for microtubules in the control of axon outgrowth is well supported by the literature. Changes in the dynamic properties of the neuroblast microtubule cytoskeleton are achieved by various mechanisms that rely on, among other processes, changes of the a-and b-tubulin isotype composition of the microtubules. Yet, the way in which specific aor b-tubulin varieties are combined and how these are incorporated into the existing tubulin pool during neuronal differentiation is still unknown. Tubulin cofactors, originally discovered as proteins required for proper tubulin folding and heterodimer formation (Campo et al.