Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

Susanna C. Concilio; Hristina R. Zhekova; Sergei Y. Noskov; Stephen J. Russell

doi:10.1371/journal.pone.0229085

Peer Review History

Original SubmissionDecember 27, 2019
24 Jan 2020 Decision Letter - Claudio M. Soares, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-19-35941 Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS) PLOS ONE Dear Dr. Russell, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses all the points raised by the reviewer. Reducing the text in selected places would improve the manuscript. We would appreciate receiving your revised manuscript by Mar 09 2020 11:59PM. 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Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. 3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The current manuscript by Dr Concilio and colleagues examines the functional parameters of several species’ NIS proteins, and models structural components of them. This is an interesting study that I think merits publication, albeit the data are slightly ‘flat’ in terms of the lessons we learn about iodide transport (as well as of related compounds) in the various species studied. However, this is an extremely thorough body of work, considering multiple compounds in multiple species. This is the kind of manuscript that will provide source data for scientists working in the field to pore over and use almost as a reference text, and hence I believe it will be well cited. One philosophical point: the relationship between substrate transport efficiency and iodide content in the environment may be less likely to reflect the comparative protein structure of NIS, and any evolutionary adaptations in terms of amino acid sequence, and more likely to reflect NIS expression levels and subcellular localisation. This point should be addressed. In terms of specific criticisms of the work, there aren’t many as the findings are straightforward and the systems used are well characterised. I could quibble about the choice of cell lines used (HeLa and HEKs), both of which are human and non-thyroidal. It is thus possible that the zebrafish NIS gene is different in iodide transport to the human gene simply because it is being tested in a human and not zebrafish setting. Furthermore, human proteins known to bind NIS and alter its function may not interact with e.g. zebrafish NIS in the same way. Although it is not feasible to repeat the experiments in zebrafish and minke whale cell lines, the authors should comment. Small points: 1. I'm not sure the manuscript as submitted matches the standard format of PLOS One papers. It may be my naivety but I was not sure that Figure legends should be embedded in the Results section? 2. The paper is too long, and a lot of the experimental detail can be condensed, and the Discussion cut by 50%. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0229085.r001
Revision 1
28 Jan 2020 Author Response We greatly appreciate the timely manner in which this review was conducted. We thank the editor-in-chief and Dr. Soares for their role in this process and assistance with the submission process. We also thank the reviewer for his/her detailed reading of our manuscript and his/her assessment of the strengths and weaknesses, as well as insightful suggestions. We have edited the manuscript to adhere to PLOS One’s style and requirements. We have run our figures through the Preflight Analysis and Conversion Engine (PACE) and they meet PLOS One’s publication standards. We have also shortened the Materials and Methods, Results, and Discussion sections as much as possible, per Reviewer 1’s recommendation. In regards to Reviewer 1’s specific comments, we have addressed the two major concerns with additional text in the manuscript. 1) Reviewer 1: “[T]he relationship between substrate transport efficiency and iodide content in the environment may be less likely to reflect the comparative protein structure of NIS, and any evolutionary adaptations in terms of amino acid sequence, and more likely to reflect NIS expression levels and subcellular localisation. This point should be addressed.” To expand upon our addition to the discussion about this point, we believe our results are indicative of fundamental attributes of the NIS proteins examined in this study as we made every attempt to equalize cell surface expression both during the experiment via the creation of cell lines with near-identical expression and after the experiment by normalization of uptake values to expression levels as determined by flow cytometry of transfected and transduced cell lines. Any differences in substrate transport observed should be the result of inherent protein function rather than differences in protein maturation, cell surface expression, or subcellular localization. 2) Reviewer 1: “Furthermore, human proteins known to bind NIS and alter its function may not interact with e.g. zebrafish NIS in the same way. Although it is not feasible to repeat the experiments in zebrafish and minke whale cell lines, the authors should comment.” We cannot deny the possibility that minke whale NIS and zebrafish NIS may have altered function due to being tested in a human cell environment. However, two points support our results and conclusions despite the potential human NIS bias: 1) As mentioned in the updated discussion, to date, there are no cellular factors known to bind or interact with NIS which affect the ion transport function. Two papers have reported NIS interacts with leukemia-associated RhoA guanine exchange factor (LARG) (DOI:10.1158/0008-5472.CAN-12-0516 and DOI: 10.1158/0008-5472.CAN-18-1954). However, this interaction was not shown to have any affect upon NIS transport activity and is considered a nonpump function of NIS. 2) Figure 2E and 2F indicates that human-, minke whale-, and zebrafish NIS are capable of transporting iodide to the same degree, suggesting there is no restriction of minke whale- or zebrafish NIS function in human cells. We also acknowledge that this manuscript does not provide experimental evidence of a mechanism for the observed differences, but we are confident that the advances we offer will be the source of much discussion and future work in the NIS field. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0229085.r002
30 Jan 2020 Decision Letter - Claudio M. Soares, Editor Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS) PONE-D-19-35941R1 Dear Dr. Russell, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. With kind regards, Claudio M. Soares, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript has been shortened, and some points made clearer/discussed more comprehensively. Thank you for addressing my points. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No https://doi.org/10.1371/journal.pone.0229085.r003
Formally Accepted
13 Feb 2020 Acceptance Letter - Claudio M. Soares, Editor PONE-D-19-35941R1 Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS) Dear Dr. Russell: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Claudio M. Soares Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0229085.r004

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