Abstract
Crosstalk between the actin and microtubule cytoskeletons underlies cellular morphogenesis. Interactions between actin filaments and microtubules are particularly important for establishing the complex polarized morphology of neurons. Here, we characterized the neuronal function of growth arrest‐specific 2‐like 1 (Gas2L1), a protein that can directly bind to actin, microtubules and microtubule plus‐end‐tracking end binding proteins. We found that Gas2L1 promotes axon branching, but restricts axon elongation in cultured rat hippocampal neurons. Using pull‐down experiments and in vitro reconstitution assays, in which purified Gas2L1 was combined with actin and dynamic microtubules, we demonstrated that Gas2L1 is autoinhibited. This autoinhibition is relieved by simultaneous binding to actin filaments and microtubules. In neurons, Gas2L1 primarily localizes to the actin cytoskeleton and functions as an actin stabilizer. The microtubule‐binding tail region of Gas2L1 directs its actin‐stabilizing activity towards the axon. We propose that Gas2L1 acts as an actin regulator, the function of which is spatially modulated by microtubules.
Highlights
The cytoskeleton is a key player in cellular morphogenesis, as it provides cells with structural support and acts as a scaffold for organelle positioning
To determine whether growth arrest-specific 2-like 1 (Gas2L1) plays a role in neuronal development, we examined the effects of Gas2L1 depletion and overexpression on axon development in dissociated primary rat hippocampal neurons
Neuronal polarity was not affected by the loss of Gas2L1, as evidenced by staining of the axon initial segment marker TRIM46 in neurons depleted of Gas2L1 (Fig 1B) [22]
Summary
The cytoskeleton is a key player in cellular morphogenesis, as it provides cells with structural support and acts as a scaffold for organelle positioning. An example of a process where cytoskeletal filaments play intricate roles is neuronal development. Developing neurons undergo extensive cell shape changes, which are coordinated by guidance cues relayed to the actin and microtubule (MT) cytoskeletons The crosstalk between MTs and actin plays an essential role during axon maturation (reviewed in Refs [2,3,4]). At the tips of axonal processes, specialized structures called growth cones determine the direction and rate of axon advance. Axon branching is believed to start with the formation of an actin patch along the axon, either de novo or as a remnant of a pausing growth cone (reviewed in Refs [5,6]). At the site of branch formation, newly generated dynamic MT plus ends are stabilized on the actin patch to initiate a new branch
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
