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When one Workshop closes, a Webinar opens…

Posted by , on 15 October 2021

Workshop vs. Webinar

In April 2020, I should have attended The Company of Biologists Workshop “The Cytoskeletal Road to Neuronal Function”. If only there was not the beginning of the SARS-CoV-2 pandemic. The Workshop was ultimately canceled, however the organizers suggested to us (the enthusiastic and disappointed participants) to initiate a Webinar as a virtual platform for the neuronal cytoskeleton research community. I and four other participants (Satish Bodakuntla, Meng-meng Fu, Oliver Glomb and Lisa Landskron) volunteered as organizers, and this is how “The Cytoskeleton of Neurons and Glia” Webinar was established in April 2021. Since then, we hosted more than twenty diverse and inspiring speakers. On October 7th our efforts reached a milestone – the twelfth Webinar marked six months of its existence!

Actin monomers as cellular cobblestones

I wrote this Node inspired by one of our speakers – Dr. Eric Vitriol. He presented a work from his Lab focusing on how actin dynamics are affected by actin monomers in neuronal cells. But first, let us take one step back and borrow the cytoskeletal road metaphor from The Company of Biologists workshop. Imagine a trail made of cobblestones, assembling underneath your feet and in front of you while you are walking. This trail will fall apart at the back once it is no longer needed. Next, imagine the cobblestones are self-aware of their numbers, and they will never start making the trail unless they “know” there is a sufficient number of them to start the construction (“critical concentration”). Additional factors like a solid ground to build on, stabilizing mortar, continuous supply of high quality cobblestones, all facilitate the trail assembly. While a self-aware and self-building trail is still far from our reality, practically all cells in our bodies have plenty of “cobblestones” called actin monomers. The monomers are present way above the critical concentration and can assemble into trails and many different cellular structures. As a matter of fact, with such a good supply of actin monomers why not building all the time?!? Well, cells have figured a way to protect themselves from an energy-costly unproductive actin assembly. This is achieved by sequestering actin monomers via another molecule called Profilin (PFN), that will release the “cobblestones” once there is a “construction permit”.

Profilin, actin monomers and neurons

In cells with neuronal origins, the team of Dr. Vitriol studied how different actin structures assemble from a common monomer pool and how Profilin 1 (PFN1) is influencing this process. They varied the concentration of PFN1 and induced cellular shortage, normal levels, or excess of PFN1. In those three conditions, they analyzed two established actin assemblies (branched Arp2/3-mediated and linear Mena/VASP based) at a highly dynamic part of the cell called leading edge. The cells responded with downsizing actin assembly throughout the cell when there is a shortage of PFN1. In addition, the lack of PFN1 repositioned the Arp2/3 nucleator complex towards the center of the circular cells, and reduced Mena/VASP function, ultimately disrupting the architecture of the leading edge. At low concentration of PFN1 cells seem to employ a mechanism to be resourceful and favor linear networks constructions. Abundance of PFN1 signals that both linear and dendritic actin networks can be reestablish. You can find more details in the paper published in 2020 in Current Biology, with Dr. Kirsten Skruber as a first author (1). This study provides us with a glimpse on how mammalian cells reshape actin assemblies when they face challenging situations when the concentrations of a major “guardian” and nucleators of the actin building blocks are changed. These disturbances must come at high costs for cell fitness, especially in long-lived, specialized cells like neurons. And while short term each cell has certain capacity to cope with different intra- and extracellular challenges, long-term exposure to the same “stretch” will eventually lead to neuronal dysfunction.

Mutations in PFN1 are direct cause of a late onset, incurable neurological disorder called amyotrophic lateral sclerosis (very recent review from another speaker in the Webinar series Dr. Kai Murk (2)). In addition, decreased levels of PFN2 were detected in cells from patients with Charcot Marie Tooth disease – genetically heterogeneous disorder affecting the peripheral nerves, as found by the team led by one of my PhD supervisors – Dr. Vincent Timmerman (3). Thus, the building blocks of the actin cytoskeleton are getting the closer attention they deserve, as there are plenty missing pieces in the puzzle that costs humans their health.

  1. Skruber et al., 2020, Current Biology 30, 2651-2664;
  2. Murk et al., 2021, Front. Cell Dev. Biol. 9, 681122;
  3. Juneja et al., 2018, J Neurol Neurosurg Psychiatry 89, 870-878.

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