Biology subjects

Minegishi, T.

Publications and source records attributed to Minegishi, T..

4 recordsLinked to original sources

bioRxiv2026

Adhesion-clutch drives three-dimensional axon outgrowth

Axon outgrowth requires forces generated by the growth cone. A key model explaining this force generation is the adhesion-clutch mechanism, in which adhesion and clutch molecules convert backward movement of actin filaments into the force that drives axon outgrowth. However, this mechanism has not been validated in three-dimensional (3D) environments. Additionally, a recent study reported that inhibiting actin dynamics or the cell adhesion molecule integrin did not affect axon outgrowth in a 3D collagen gel, challenging the adhesion-clutch paradigm. Here, we show that the adhesion molecule N-cadherin and the clutch molecule shootin1a form a non-integrin adhesion-clutch in a 3D environment containing an appropriate adhesive substrate, N-cadherin. We detected forces produced by growth cones when N-cadherin was present. Furthermore, inhibition of N-cadherin, shootin1a or actin dynamics suppressed 3D axon outgrowth. Our findings demonstrate that the adhesion-clutch is critical machinery for 3D neural network formation under the regulation of specific adhesions.

neuroscience↗

bioRxiv2024

Cell morphogenesis via shape-guided self-propelled treadmilling actin waves

Cells frequently undergo spontaneous morphogenesis, yet the underlying mechanisms remain incompletely understood. While actin filaments are central to cell morphogenesis and are typically regulated by biochemical signaling, cells can form protrusions even without clear external cues, suggesting the existence of intrinsic physical mechanisms. Here, we report that actin filaments undergo directional movement driven by treadmilling, an ATP-fueled polymerization-disassembly cycle intrinsic to actin. These Self-propelled Treadmilling Actin filaments (SpTAs), exhibit stochastic yet directional motion, in a manner similar to self-propelled "particles" rather than the previously reported reaction-diffusion "waves". SpTA arrival at the cell periphery drives membrane protrusion by orienting their polymerizing ends outwards. This SpTA accumulation, guided by nascent membrane curvature, further amplifies protrusion growth and expansion, driving cellular polarization for migration. Our findings establish actin filament as a novel class of active particle, providing a fundamental physical framework for understanding how molecular-scale motion leads to higher-order organization in living systems.

cell biology↗

bioRxiv2023

Mechanical Netrin-1-DCC Coupling Mediates Netrin-1-induced Axonal Haptotaxis

The growth cone, a motile structure located at the tip of growing axon, senses extracellular guidance cues and translates them into directional forces that drive axon outgrowth and guidance. Axon guidance directed by chemical cues on the extracellular adhesive substrate is termed haptotaxis. Recent studies reported that netrin-1 on the substrate functions as a haptotactic axon guidance cue. However, the mechanism mediating netrin-1-induced axonal haptotaxis remains unclear. Here, we demonstrate that substrate-bound netrin-1 induces axonal haptotaxis by facilitating physical interactions between the netrin-1 receptor, DCC, and the adhesive substrates. DCC serves as an adhesion receptor for netrin-1. The clutch molecule shootin1a interacted with DCC, linking it to actin filament retrograde flow at the growth cone. Speckle imaging analyses showed that DCC underwent either grip (stop) and retrograde slip on the adhesive substrate. The grip state was more prevalent on netrin-1-coated substrate compared to the control substrate polylysine, thereby transmitting larger traction force on the netrin-1-coated substrate. Furthermore, disruption of the linkage between actin flow and DCC by shootin1 knockout impaired netrin-1-induced axonal haptotaxis. These findings indicate that the directional force for netrin-1-induced haptotaxis is exerted on the substrates through the mechanical coupling between netrin-1 and DCC which occurs asymmetrically under the growth cone.

cell biology↗

bioRxiv2023

Mechanical signalling via membrane tension drives saltatory neuronal migration

Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated mechanosensitive ion channels and triggered Ca2+ influx, leading to actomyosin activation at the rear of the cell. Blockade of this signaling pathway disturbed somal translocation, thereby inhibiting neuronal migration in three-dimensional environments. Thus, mechanical signaling through plasma membrane tension and mechano-channels links the leading process extension to somal translocation, allowing rapid and saltatory neuronal migration.

cell biology↗