Dwilfand

Feedback (by Manvita Mareboina)

·       I really liked the topic and found it very interesting. My number one comment would be to add more information to make the article more specific and clearer on the topic.

·       Including the main purpose of the Actin Depolymerizing factor in the first intro paragraph would be very helpful to understand what it is from the very beginning. However, the structure of going from intro to structure to action and regulation was very nice.

·       Maybe describing in the structure how the central helix and stability aid in its function will connect the mechanism and structure section better.

·       Although it is stated what the family of this factor includes, it is hard for the reader to know what that means so listing what those molecules such as ADF and Cofilin-1 are may be more helpful.

·       Under regulation, the sentence is very vague in saying that it is “regulated by many factors within the cell.” Perhaps expanding on what these factors are or how they regulate actin depolymerization specifically will help give the reader a clearer understanding. Include information on what the conserved serine is and how dephosphorylation and phosphorylation work to activate and inactivate the factor.

·       There is no information that is redundant, however information should be added to specify key words in each subsection.

·       Overall the organization is good, there is no bias and the topic is interesting but adding more information will make this a better article. Having more references will really help with adding more information. Everything written is good and unbiased, but having more information that gets into the specifics of each subsection (including more forms of regulation) would be very helpful.

-I think it would help to clarify a lot of the terminology throughout. For example defining terms such as depolymerizing, elaborating on the specific regulations and mechanisms of action, and expanding on each of the subtopics such as pH changes and activation would be very helpful.

-For the intro, talk more about actin in terms of its main function so that the reader can dive into the topic immediately knowing what the main idea of what the depolymerizing factor is. What is the purpose of the importance of this factor? (this will also make the paper more interesting from the start!).

-For the structure portion, talk abut the different specific mechanisms that are involved in creating this structure or how this structure really helps aid in the function of the actin depolymerizing factor. Overall, why is this structure relevant or what can it help the factor do? Maybe talking about how manipulations in this structure affect function will also make it more helpful to the reader to understand the importance of its particular structure. I also recommend having a picture that exemplifies each point about the structure of the Actin Depolymerizing Factor. It would really help the reader.

-For the mechanism of action section, it was organized really well but maybe talking more specifically about the mechanism of action such as describing what phailoid is will make the paper more clear.

-For the regulation section, maybe adding more on activation would be better. What is the relevance of serine? how does this affect dephosphorylation? Having more specifics in this section will make it more affective in terms of understanding the main purpose of the regulation of this factor.

-Overall, the structure was very good and the topic was very interesting,but my main suggestion would be to more clearly define certain terms and try to add more information in specific sections such as the introduction and structure and connect the structure to function. The topic was very interesting!

Actin Depolymerizing Factor Review -- Marie Bae

Hi, interesting article! I enjoyed reading about it, and you had some really good information! I really liked how you organized the sections, as they flow well! If you want to add sections, I thought that adding a Function section before "Structure" or adding the functional significance in the intro (more on this in "Intro") might be a useful piece of information. My main suggestion would be to add some more information about actin depolymerizing factor (I'll be referring to it as ADF from now on), and here are some specific suggestions/comments:

• Intro:
  • Maybe going into the intro, you can clarify what “depolymerizing” means and what actin is involved with? I feel that getting into what actin is and briefly mentioning what an ADF does may help you expand into the functional significance (Is it in neuronal development? If so, elaborate.) of ADF. The lead introduction sentence told me "What an 'actin depolymerizing factor' is," but I thought that describing "depolymerizing" in a different way may be better to explain to a general audience about what ADF does, which I assume is cleaving actin polymers into monomers?
  • Grammar: This is more of a personal preference, but I would suggest saying that ADF is "a family of proteins involved with the depolymerization of actin polymers" for better grammatical flow.
• Structure:
  • In this section, I thought it might be helpful to explain the “characteristic fold” of the five beta sheets and four helices and relate it to why that particular fold contributes to the mechanism, and you can directly transition into the “Mechanism of Action.” I also thought that an image showing the structure of ADF and distinguishing these characteristic beta sheets and alpha helices with different colors would be really helpful here.
  • Grammar(?): “plays a role in both structural stability ‘and’ F-actin binding”? If not, I was a bit confused as to what "both" was referring to.
    • Also, maybe you can briefly explain what F-actin is? (Edit suggestion: "...binding of F-actin, a(n) ______________.")
• Mechanism of Action
  • I definitely thought that you had a lot of good information here about the mechanism! I really liked how you described how actin was destabilized from the binding of the F-actin subunits with ADF.
  • Maybe you can briefly mention what phailoid and cofilin are? (Editing suggestion: "...to bind phailoid, a _____________ that is necessary...")
• Regulation
  • (I'm assuming the image you added was for regulation) I thought it would be great if you could mention tropomyosin within the text of your article. Is it part of "Activation of Actin Depolymerizing Factor," or is it a new way to regulate ADF function by binding to actin's F site?
  • pH changes
    • "so therefore" just seemed a little bit redundant grammar. Maybe just use ", so" or "; therefore"?
  • Activation of Actin Depolymerizing Factor
    • Maybe you can allude to the conserved serine in the structure, too! I had a question about the serine: Is it part of a catalytic sequence? What makes that serine particularly important?
• References:
  • I remember Dr. Tienson mentioning ten sources by the end of the finalized article, but I may be wrong! Otherwise, based on the titles, that most of the sources have DOIs, and that you explained that the mechanobio.info website (the source without a DOI) is a good source for a broad overview of the mechanism and that you may refer to cited articles for more information, I thought your sources were reliable and relevant. I couldn't find the title for the citation #7, however, so I am unsure about its relevance. I suggest using the "Cite" function via "Visual Edit." I found this really helpful when adding my sources because all I had to do was enter the URL (or DOI) of an article and they would automatically cite with title, author,...!

Overall, I thought your article was really interesting. The content in each section seemed appropriate, and I didn't think there was any redundant or off-topic information. I did not detect any bias or personal opinions, which is great because I feel that I was given an objective description of ADF. I thought each section had a pretty good flow, with the minor exception of Tropomyosin in the image not being mentioned anywhere in the text. This is good article with great information, but I felt that you may be able to add some more information. Thanks for a great article about actin depolymerizing factors!

Sincerely,

Marie Bae