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Lesson 6 of Cell Signaling & Motility – Cytoskeleton II: #TUBiol3373

Stephen J. Williams, Ph.D.

In this lesson we will go over the biochemical makeup and formation of various actin containing cellular structures involved in cellular motility, structure, as well as the dynamics of muscular contraction.  The lesson had been put on your Canvas and I am emailing you the Google Docs version.  If you are having problems downloading you can download here (I believe maybe the Canvas version had problems with embedding videos properly so that is why I am sending you also by email)

Download Below

cell signaling 6 lesson 2020

After opening the powerpoint (or Google Doc) please review with the following notes which highlight some concepts as well as some reviews and reminders of past lectures.  It may be handy to also have lecture 5 handy if you need to refer to it.  In between some sections there will be polls (really multiple choice quizzes DON’T WORRY you will not be graded on them but they are for your benefit.  There will also be a section under Comments all the way at the end and at the last quiz where you can also ask questions.

Remember you can always email me or Tweet me any questions @StephenJWillia2 using the hashtag #TUBiol3373.

In addition you can also leave comments at the very bottom which can be answered.

Slide 2 of lesson 6 is a refresher of the end of our last lecture, talking about Actin Binding Regulatory Proteins.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The picture above shows a brief review of some of the structures and actin binding proteins involved in helping to form these actin filament structures (like filamin in cross linked structures, profilin which binds the actin monomers [G-actin] and helps with addition of these monomers to the leading plus end.

*** Remember G-actin (Globular Actin) is the monomer and F-actin (filamentious actin) is the polymerized actin strand [filament]

Also remember from the last lecture that G-Actin as monomer has affinity for ATP {Adenosine triphosphate} and these G-Actin-ATP will be able to polymerize to form the F-Actin form.  Also F-actin can then hydrolyze the ATP to ADP and inorganic phosphate.  At this point the actin-ADP unit looses affinity for the remaining F-Actin chain and depolymerization can occur

 

An event referred to as TREADMILLING or when the G actin units are removed from minus end and added to the plus (or growing barbed) end

Also remember that there is a critical concentration of G-Actin-ATP needed for bypassing the lag phase of nucleation before the elongation phase and the rate of addition to the plus end is faster than addition to minus end and greater than the rate of depolymerization at the minus end

Cell Structures That Involve Actin (see links for more information)

  1. filopodia
  2. parallel actin bundles
  3. actin cortex
  4. lamellipodia
  5. stress fibers
  6. microvilli
  7. contractile ring in cytokinesis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nucleating proteins Arp (actin related protein and Formins

Arp ====> formation of lamellipodia

Formins ====> formation of stress fibers

Process involving formins starts with a signaling event by activation of a G-protein, the GTP binding protein Rho

Rho is a subfamily member of the Ras superfamily.  The Rho family consists of cdc42, rac1, and RhoA (we will discuss at a later date).  Rho acts like G proteins, as a molecular switch.

Note that just like the Ras member of G-proteins and the Ras GTP/GDP cycle, the Rho activation, deactivation cycle also depends on GEFs [Guanine nucleotide exchange factors] and GAPs [GTPase activating proteins] and also GDIs [guanine nucleotide dissociation inhibitors which we will discuss later but involved in preventing Rho diffusion in the cell, acting as a tether].

Myosin and Motor (muscle) Function; Neuromuscular junctions, the sarcoplasmic reticulum and Ohhh the plethora of signaling events

In this section, from slides 29 to 54, we talk about myosin and the interactions between myosin and actin in formation of the contractile unit of the muscle (skeletal).

We also talk about some familiar signaling events, in particular the neuromuscular junction.

At this junction is a special type of acetylcholine receptor

Remember we talked about two types of acetylcholine receptors:

  1. muscarinic receptors – typical GPCRs that tranduce the signal via Gi or Gq depending on the muscarinic subtype
  2. nicotinic receptors – these are ligand {receptor} operated channels and when activated opens a Na+ channel which leads to depolarization

 

Now the depolarization activates another set of channels, the voltage operated calcium channels so we have two types of ion channels: Receptor {ligand} operated channels and Voltage operated channels.  These are sometimes abbreviated as ROCs and VOCs.

The unit of the myofibril on the contactile unit of the skeletal muscle is the sarcomere and upon the calcium transient, the sarcomere shortens with the two z-disks moving closer to each other as shown in the video in the lecture.

Also briefly review the introduction part on microtubules. We will finish that next week. Note that the microtubule is comprised of the protein tubulin, which is another GTP binding protein.

For other articles and more information please see

Lesson 5 Cell Signaling And Motility: Cytoskeleton & Actin: Curations and Articles of reference as supplemental information: #TUBiol3373

Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

Identification of Biomarkers that are Related to the Actin Cytoskeleton

 

 

 

 

 

 

 

 

 

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