An Integrated Cytoskeletal Model of Neurite Outgrowth

Abstract

Neurite outgrowth underlies the wiring of the nervous system during development and regeneration. Despite a significant body of research, the underlying cytoskeletal mechanics of growth and guidance are not fully understood, and the relative contributions of individual cytoskeletal processes to neurite growth are controversial. Here, we review the structural organization and biophysical properties of neurons to make a semi-quantitative comparison of the relative contributions of different processes to neurite growth. From this, we develop the idea that neurons are active fluids, which generate strong contractile forces in the growth cone and weaker contractile forces along the axon. As a result of subcellular gradients in forces and material properties, actin flows rapidly rearward in the growth cone periphery, and microtubules flow forward in bulk along the axon. With this framework, an integrated model of neurite outgrowth is proposed that hopefully will guide new approaches to stimulate neuronal growth.

The G protein‐coupled oestrogen receptor, GPER1, mediates direct anti‐inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert

“…61 Interestingly, vinculin is involved with anchoring actin to the membrane and plays a role in neurite extension and cell motility. 62,63 Hence, the results obtained in the present study further suggest that GPER1 may mediate the effects of E 2 on neurite outgrowth in hfNBMs, as reported previously. 34 Moreover, our findings appear to be in agreement with the demonstration that GPER1 stimulation with E 2 in different cellular systems (eg, breast cancer cells) promotes the formation of focal adhesions leading to the reorganisation of actin stress fibres and enhanced cellular adhesivity.…”

“…In this regard, recent studies have identified a family of adhesion GPCRs, comprising a large panel of 30 homologues within the GPCR superfamily displaying receptivity toward mechanical cues . Interestingly, vinculin is involved with anchoring actin to the membrane and plays a role in neurite extension and cell motility . Hence, the results obtained in the present study further suggest that GPER1 may mediate the effects of E 2 on neurite outgrowth in hfNBMs, as reported previously .…”

Cofilin, a Master Node Regulating Cytoskeletal Pathogenesis in Alzheimer’s Disease

“…In axons, the plus end is directed away from the cell body toward the presynaptic terminal, whereas dendrites possess mixed populations of plus and minus ends pointing away from the cell body [49]. Unlike the actin network, microtubules are not enriched at synaptic sites but can transiently assemble inside dendritic spines in an activity-dependent manner [47,50,51]. The microtubule-associated proteins (MAPs), which include MAP1A, MAP1B, MAPT2, MAP4, and tau, regulate the assembly, stability, and disassembly of the microtubule network [48,52].…”

Mms19promotes spindle microtubule assembly in neural stem cells through two distinct pathways

“…Interestingly, such a MT bundling activity seems also crucial for neurite outgrowth, because 447 the initial stage of this process involves bundling of MTs (Miller and Suter, 2018). This would 448 explain why this process is delayed or blocked in most Mms19 P neurons ( Fig S8).…”