the biofixer

What makes you move? The Myosin Paradigm and the Power Stroke

          The movement of your eyes as you  scan your friends’ posts at the moment, the clicks of your fingers as you choose relevant links that suit your interest or even the perplex of your Zygomaticus major and minor along with the rest of muscles involve in smiling as you saw your crush dear photo flashing across the screen - there must be something that drive such motions. What powers your every move  at daily occasion from walking, writing, eating or even the subtle laugh is primed by the simple yet efficacious molecule. Commendably, whatever your situation at this instance, all of the varied movements you are making right now are powered by this molecule named Myosin.  Whether voluntarily or involuntarily, it’s the Myosin that sets you on the Go! 

So whats with Myosin then? Myosin is a molecule-sized muscle that uses chemical energy to perform a deliberate motion. Myosin captures a molecule of ATP, the molecule used to transfer energy in cells, and breaks it, using the energy to perform a “power stroke.”  Myosin is composed of several protein chains: two large “heavy” chains (color red) and four small “light” chains (colors orange and yellow). Each myosin performs only a tiny molecular motion. But by working together, the tiny individual power stroke of each myosin is summed to provide macroscopic power in our familiar world.

Myosin requires huge amounts of ATP when muscles are exerted. Say for instance your in the mood for a run. When you start running, the supply of ATP in your muscles lasts only about a second. Then, the muscle cells shift to phosphocreatine, a backup source of energy, which can be converted quickly into about 10 seconds worth of ATP. Then, if you are still running full tilt, your muscles start using glycogen, a molecule that stores glucose. This lasts for a minute or two, building up toxic acids as the sugar is used up. Then, the sprint is over and you have pushed your muscles to the limit. If, however, you slow down and pace yourself, your muscles can perform much longer. The blood vessels will dilate and your heart rate will increase, bringing twenty times as much blood through the muscles. Your muscle cells can then use this extra oxygen to produce far more ATP from the sugar in glycogen. Instead of collapsing after a short sprint, you now have the resources for a mountain hike or a marathon.

So where does the mighty Myosin takes into play?. We do know that ATP is the energy currency of the cell. ATP contains a key phosphate-phosphate bond that is difficult to create and is used to power many processes inside cells. You might be surprised to find, however, that breakage of this phosphate-phosphate bond is not directly responsible for the power stroke in myosin. Instead, it is release of the phosphate left over after ATP is cleaved that powers the stroke. Think of myosin like an arm that can flex towards you or push away. The cleavage of ATP is used in a priming step. When ATP is cleaved, myosin adopts a bent, flexed form. This prepares myosin for the power stroke. The flexed myosin then grabs the actin filament ( and release of phosphate snaps it into the straight “rigor” form. This power stroke pushes the myosin molecule along the actin filament. When finished, the remaining ADP is replaced by a new ATP, the myosin lets go of the actin filament. Then, it is ready for the next stroke. As this process goes on and on, you are abled to do movements just like your extraocular muscles do move your eyes as you read this post.

photo Credit: David Goodsell

Decisive Role in Cell Division Identified for Centrosomal Protein

The answer to an elusive question about signaling in chromosome distribution and separation has been provided by the discovery of a key role for a centrosomal protein kinase. The kinase also has potential importance as a new candidate among cell division factors being targeted in the development of drug treatments for cancer.

      The protein kinase Nek9 has been highlighted as an essential and decisive factor in a pathway involved in ensuring efficient and accurate movement of chromosomes during cell division. γ-tubulin recruitment to and accumulation at the centrosome during the centrosome maturation stage of mitosis is known to depend on the adaptor protein NEDD1/GCP-WD and to be controlled by the kinase Plk1. Surprisingly, and although Plk1 binds and phosphorylates NEDD1 at multiple sites, the mechanism by which this kinase promotes centrosomal recruitment of γ-tubulin has remained elusive. Using Xenopus egg extracts and mammalian cells, the scientists found that Nek9, a kinase required for normal mitotic progression and spindle organization, phosphorylates NEDD1, driving its recruitment and thereby that of γ-tubulin to the centrosome. This role of Nek9 requires its activation by Plk1-dependent phosphorylation.

       Errors in chromosome distribution cause many spontaneous miscarriages, some genetic defects such as trisomies, and are related to the development of tumors. Nek9 exerts its action between two molecules, Plk1 and Eg5, of interest as antitumoral agents and for which inhibitors are already in advanced stages of clinical trials. Nek9 could well be added to the list of cell division target candidates.

      Without Nek9 the spindle would not form properly and cell division would be hindered, the cells would die or cause aneuploidies, with unequal distribution of chromosomes, an event that is common in tumors. 

(Source: Joan Roig et al., 2012. Nek9 Phosphorylation of NEDD1/GCP-WD Contributes to Plk1 Control of γ-Tubulin Recruitment to the Mitotic Centrosome. Current Biology)