FIRST PERSON

First person – Lizbeth de la CruzFirst Person is a series of interviews with the first authors of aselection of papers published in Journal of Cell Science, helpingearly-career researchers promote themselves alongside their papers.Lizbeth de la Cruz is first author on ‘Plasmamembrane processes aredifferentially regulated by type I phosphatidylinositol phosphate5-kinases and RASSF4’, published in JCS. Lizbeth is a Postdoc inthe lab of Bertil Hille at the University of Washington, School ofMedicine, Seattle, WA, where they investigate signaling bymembrane phosphoinositide lipids.

How would you explain the main findings of your paperin lay terms?The cell is surrounded by a membrane made of lipids and proteins.When I was a PhD student, I became aware that some ofthe membrane lipids regulate and are required for activity ofthe membrane proteins. These regulatory lipids are calledphosphoinositides. Should we imagine that they govern proteinsuniformly all over the extent of the cell membrane, or instead arethey somehow segregated in local functional domains that eachregulate their own target proteins? To explore this question, westudied three different interventions that change phosphoinositidesin the membrane.We asked whether each intervention regulated twomembrane processes equivalently. We needed to use different kindsof microscopy, and calcium and current measurements to assay themembrane processes. We found that when phosphoinositides wereincreased, the two membrane processes were differentially affecteddepending on which intervention was used. This suggests that thehypothesis of local segregated action of phosphoinositides betterreflects reality than the hypothesis of an uniform global action.

Were there any specific challenges associated with thisproject? If so, how did you overcome them?The project required long experiments to compare responses amongseveral groups of cells on the same day. It took systematic analysisand multiple readouts of the levels of PtdInsP2 to understand that wewere dealing with a fine regulation of a well-known signaling lipid.The key was to work as a team with each collaborator an author onthis article.

When doing the research, did you have a particular resultor ‘eureka’ moment that has stuck with you?When we started the project, we tested only one isoform of thePtdInsP 5-kinase (PtdInsP5K) we were interested in, and our resultsappeared to contradict previously published data. I dove into theliterature and discovered one study suggesting that some of theseeffects might be isoform specific.When we tested several isoforms ofPtdInsP5K, we found that membrane processes were differentiallyregulated by each isoform. This eureka moment not only resolved theapparent contradiction between our results and prior work, butopened up a new understanding of how specificity is achieved withinphosphoinositide modulation of plasma membrane signaling.

Why did you choose Journal of Cell Science for your paper?We chose this journal because of its strong publication record andrelevant topical focus. In fact, the paper that inspired the turningpoint for our project was a 2011 publication of the Journal of CellScience (Calloway et al., 2011).

Have you had any significant mentors who have helped youbeyond supervision in the lab? How was their guidancespecial?Yes, during my training as a researcher I have met great scientists.They taught me how important it is to find a balance between beinga researcher, a wife and a mother. Jill Jensen and Bertil Hille, co-authors of this paper, are great examples of my model scientists.They showed me that science is more fun when it is balanced with ahealthy sense of community and family.

What motivated you to pursue a career in science, and whathave been themost interestingmoments on the path that ledyou to where you are now?Since I was a child I have been curious about nature and howit works. My career in science allows me to ask questions andpursue their answers, each day learning something new andunderstanding better how things work. When I took my firstacademic stay out of Mexico as a graduate student, I metindividuals with the same passion and drive for science andrealized this could be my career.

Lizbeth de la Cruz

Lizbeth de la Cruz’s contact details: University of Washington, School of Medicine,Physiology and Biophysics, G-424, Box 357290, Seattle, WA 98195-7290, USA.E-mail: ddlc@uw.edu

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© 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2020) 133, jcs243147. doi:10.1242/jcs.243147

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Who are your role models in science? Why?As I mentioned above, Bertil Hille and Jill Jensen are my rolemodels. Both share a strong criticism for each experiment that

teaches me to increase the quality of my experiments every day. Atthe same time, they are open-minded and keep up-to-date, both greatqualities to do science. Finally, Jill Jensen has been my role modelto be a great scientist and mother.

What’s next for you?I am continuing my training with a second postdoctoral stay andhope to open my own laboratory in Mexico in a few years.

Tell us something interesting about yourself thatwouldn’t beon your CVI also love archaeology, and have attended seminars and conferencesabout Mexican archaeology. My dream is to collaborate witharcheologists on research projects.

ReferencesCalloway, N., Owens, T., Corwith, K., Rodgers, W., Holowka, D. and Baird, B.

(2011). Stimulated association of STIM1 and Orai1 is regulated by the balance ofPtdIns(4,5)P2 between distinct membrane pools. J. Cell Sci. 124, 2602–2610.doi:10.1242/jcs.084178

de la Cruz, L., Traynor-Kaplan, A., Vivas, O., Hille, B. and Jensen, J. B. (2020).Plasma membrane processes are differentially regulated by type Iphosphatidylinositol phosphate 5-kinases and RASSF4. J. Cell Sci. 133,jcs233254. doi:10.1242/jcs.233254

Localization of PtdIns(4,5)P2 using PH-PLCδ1 as a fluorescent probe.Left, bottom section at the glass-adhered basal membrane showingPtdIns(4,5)P2 at the plasma membrane and extending into filopodia andlamellipodia. Pseudo-color shows low fluorescence in purple and high inyellow. Right, a 3D reconstruction of probe fluorescence in a Z-stack of thesame cell. Note the predominant fluorescence of PH-PLCδ1in ringscorresponding to the plasma membrane around the cell (colored rings). PH-PLCδ1 fluorescence was acquired with an Airyscan confocal microscope in asingle tsA201 cell.

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FIRST PERSON Journal of Cell Science (2020) 133, jcs243147. doi:10.1242/jcs.243147

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ofCe

llScience