Review of PIP2 in Cellular Signaling, Functions and Diseases

Round 1

Reviewer 1 Report

The current manuscript is well-organized by summarizing the significance of PIP2 biology and related regulations. Thus it is suitable for publication. The manuscript (ijms-956055) covers the recent progress in the field of PIP2 lipid metabolite. In particular, authors focuse on the role of PIP2 in controlling actin reorganization and related membrane dynamic events. The list of selected references and their interpretations seem correct and nicely introduced. By comprehensivley summarizing properties of PIP2, its binding proteins, and related signaling pathways, readers would have clear insight into the significance of PIP2 biology, its regulation, and associated diseases. Overall, I strongly believe this manuscript would make good contribution to members of cell biology as well as general readers.

Author Response

Dear Reviewer,

Thank you very much for your encouraging remark. I really appreciate your time and effort for reviewing the manuscript. 

I am also thankful for your service to scientific community. 

I am looking forward to see the manuscript published soon. 

Best,

Kalpana

Reviewer 2 Report

The manuscript by Kalpana Mandal is focused on the role of phosphoinositides (PI) in different cellular functions, with particular focus on PI(4,5)P2. The review is interesting, and describes many aspects of PI related pathways and cellular outfits, giving the reader many useful informations.

However, before publications some criticisms have to be addressed. The paper is sloppily written, and parts of the text miss references. For example, the introduction Paragraph contains only 5 Refs despite the vast amount of reported informations about PI and PI signalling related proteins. This also recurs in other paragraphs:

-lanes 73-74;

-lanes 120-123;

- lanes 247-249;

-lanes 260-264;

- lanes 403-407.

Please fill the gaps in terms of missing References. 

Figure 1: PIP4Ks phosphorylate PI5P leading to PI(4,5)P2 (as reported in the text). In the figure, the author refers to PIP4K as PIP5KII (their original name, before the discovery that PIP4K are a completely different class of proteins than PIP5K). Moreover, the author indicates PIP4K as able to phosphorylate PI3P, which was shown always by Rameh et al. (Nature, Vol.390 pages192–196(1997), but only able to alter PI5P levels in vivo. Please correct the statement in the figure since how PI3P is converted into PI(3,4)P2 is not well understood yet.

It is particularly bothersome how the author refers to PI(4,5)P2 in the text. Since in cells exist 3 different 'forms' of PIP2, PI(3,4)P2, PI(3,5)P2 and PI(4,5)P2, the author should always use the entire name of the specific Phosphoinositide is referring to. This will avoid any misleading interpretation for the reader.

There are errors in the text:

• lane 343 : it should be PI(3,4,5)P3, not 2;
• lane 345 : correlated
• lane 238: is THE most abundant

And so on. Please carefully correct the text.

Lane 163 ECM: extracellular matrix (ECM).

Pending these recommendations, the manuscript by Kalpana Mandal could be published in IJMS.

Author Response

Dear Reviewer,

Thank you very much for handling our manuscript entitled ‘​Review of Phosphoinositides in cellular signaling, functions and diseases’. We thank the reviewers for their valuable comments, and we have revised the manuscript based on their comments. Both reviewers acknowledge that the review is interesting and comprehensively summarizes an important point forward for the field. We have taken their comments into consideration and extensively revised the manuscript. 

Here we summarize our key changes to the manuscript.

Open Review2

(x) I would not like to sign my review report
( ) I would like to sign my review report

English language and style

(x) Extensive editing of English language and style required
( ) Moderate English changes required
( ) English language and style are fine/minor spell check required
( ) I don't feel qualified to judge about the English language and style

Comments and Suggestions for Authors

The manuscript by Kalpana Mandal is focused on the role of phosphoinositides (PI) in different cellular functions, with particular focus on PI(4,5)P2. The review is interesting, and describes many aspects of PI related pathways and cellular outfits, giving the reader many useful informations.

However, before publications some criticisms have to be addressed. The paper is sloppily written, and parts of the text miss references. For example, the introduction Paragraph contains only 5 Refs despite the vast amount of reported informations about PI and PI signalling related proteins. This also recurs in other paragraphs:

We appreciate the constructive comments from the reviewer. The reviewers’ comments and suggestions have helped us to improve the manuscript. We really appreciate the time and effort had been taken to provide us detailed revision.

-lanes 73-74; Corrected

-lanes 120-123; Corrected

- lanes 247-249; Corrected

-lanes 260-264; Corrected

- lanes 403-407. Corrected

Please fill the gaps in terms of missing References. Corrected

Figure 1: PIP4Ks phosphorylate PI5P leading to PI(4,5)P2 (as reported in the text). In the figure, the author refers to PIP4K as PIP5KII (their original name, before the discovery that PIP4K are a completely different class of proteins than PIP5K). Moreover, the author indicates PIP4K as able to phosphorylate PI3P, which was shown always by Rameh et al. (Nature, Vol.390 pages192–196(1997), but only able to alter PI5P levels in vivo. Please correct the statement in the figure since how PI3P is converted into PI(3,4)P2 is not well understood yet.

Corrected

It is particularly bothersome how the author refers to PI(4,5)P2 in the text. Since in cells exist 3 different 'forms' of PIP2, PI(3,4)P2, PI(3,5)P2 and PI(4,5)P2, the author should always use the entire name of the specific Phosphoinositide is referring to. This will avoid any misleading interpretation for the reader.

We have corrected for the cases where it is not specifically shown for any of the PIP2. But id the reviewed work has specifically mentioned about PI (4,5) P2, those cases it is left as it is. In the beginning of the text we have mentioned the full name of specific Phosphoinositide, later (short name) formula had been used.

There are errors in the text:

lane 343 : it should be cc, not 2; Corrected

lane 345 : correlated Corrected

lane 238: is THE most abundant Corrected

And so on. Please carefully correct the text.

Lane 163 ECM: extracellular matrix (ECM). Corrected

Pending these recommendations, the manuscript by Kalpana Mandal could be published in IJMS.