Just came back from a RIPS, very interesting movies! They inspired me many random thoughts. However, the discussion at that time clearly went to another direction. So, I have to pour my thoughts somewhere else. If you have any idea, please do comment. Thanks!
All things below are purely based on my memory and limited reading of the focal adhesion field. If any evidence against it, please let me know :-) If you want to test my model, feel free; because I am not studying in the field of focal adhesion dynamics.
First, let me define "retrograde flow". "The flow of fluid in a direction other than normal, as in regurgitation.". It is widely used in the actin filed, as show in the diagram below. But, as far as I know, this concept has never been introduced into focal adhesions, because focal adhesions are anchored structure - how do they move, even retrograde flow? I would say that if focal adhesion proteins move "backwards" I define focal adhesion flows retrograde.
The assemble of focal adhesion has been extensively studied. With the help of super-high resolution microscopy, especially PALM, the molecular model and assemble dynamics of focal adhesions have been clearly demonstrated. However, how focal adhesions disassembled/remodeled has not been convincingly and clearly presented from the molecular level. What I am proposing here is an alternative way for focal adhesions to disassemble. Considering the normal way for focal adhesions disassembly is quite efficient and focal adhesions disassemble whenever they are no longer needed, like the left column of the following diagram.
In the alternative (right column above), inefficient focal adhesion disassembly, happens when the normal/efficient way is inhibited/disconnected/disrupted/altered - demonstrated as focal adhesion retrograde flow:
- Only happens in the disassembly phase, not the assembly phase of focal adhesion.
- It is inefficient, mainly in the recycling of focal adhesion proteins. Thus, more functional focal adhesion proteins are required to exert "normal" cellular events.
- It is bound to actin filaments, which is the driving force of retrograde flow. Any treatment disrupts actin retrograde flow should be able to disrupt focal adhesion retrograde flow. Also, any treatment disconnect the focal adhesion from the actin cytoskeleton should be able to disrupt focal adhesion retrograde flow.
- It should be possible to generate kymograph of focal adhesion retrograde flow, which can be used to study the correlation with actin retrograde flow.
- Treatments affect the stability of focal adhesions might affect the focal adhesion retrograde flow.
- The focal adhesion retrograde flow "slowly" drains the focal adhesion and causes the "shrinkage" of the size of focal adhesion.
- After photo-bleaching correction, the total amount of fluorescence from the focal adhesion retrograde flow track should stay the same during the time of retrograde flow, although the track is elongating due to the flow.
- Most of, if not all, focal adhesion proteins should be observed in the retrograde flow with similar dynamics. The ECM binding proteins should not be found in the focal adhesion retrograde flow.
Below is a diagram about how people currently think the actin/myosin network connected with the focal adhesions (this is the only reference I checked while typing this post). It is highly possible that in certain condition, some focal adhesion protein will be tightly bound to actin filaments and fades as retrograde flow ...
Science. 2007 Jan 5;315(5808):111-5.
Differential transmission of actin motion within focal adhesions.
Hu K, Ji L, Applegate KT, Danuser G, Waterman-Storer CM.
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.Cell migration requires the transmission of motion generated in the actin cytoskeleton to the extracellular environment through a complex assembly of proteins in focal adhesions. We developed correlational fluorescent speckle microscopy to measure the coupling of focal-adhesion proteins to actin filaments. Different classes of focal-adhesion structural and regulatory molecules exhibited varying degrees of correlated motions with actin filaments, indicating hierarchical transmission of actin motion through focal adhesions. Interactions between vinculin, talin, and actin filaments appear to constitute a slippage interface between the cytoskeleton and integrins, generating a molecular clutch that is regulated during the morphodynamic transitions of cell migration.
Posted 2010-3-29 by Liang C.
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