ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Lizbeth de la Cruz is first author on ‘Plasma membrane processes are differentially regulated by type I phosphatidylinositol phosphate 5-kinases and RASSF4’, published in JCS. Lizbeth is a Postdoc in the lab of Bertil Hille at the University of Washington, School of Medicine, Seattle, WA, where they investigate signaling by membrane phosphoinositide lipids.

Lizbeth de la Cruz

How would you explain the main findings of your paper in 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 of the membrane lipids regulate and are required for activity of the membrane proteins. These regulatory lipids are called phosphoinositides. Should we imagine that they govern proteins uniformly all over the extent of the cell membrane, or instead are they somehow segregated in local functional domains that each regulate their own target proteins? To explore this question, we studied three different interventions that change phosphoinositides in the membrane. We asked whether each intervention regulated two membrane processes equivalently. We needed to use different kinds of microscopy, and calcium and current measurements to assay the membrane processes. We found that when phosphoinositides were increased, the two membrane processes were differentially affected depending on which intervention was used. This suggests that the hypothesis of local segregated action of phosphoinositides better reflects reality than the hypothesis of an uniform global action.

Were there any specific challenges associated with this project? If so, how did you overcome them?

The project required long experiments to compare responses among several groups of cells on the same day. It took systematic analysis and multiple readouts of the levels of PtdInsP2 to understand that we were dealing with a fine regulation of a well-known signaling lipid. The key was to work as a team with each collaborator an author on this article.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

When we started the project, we tested only one isoform of the PtdInsP 5-kinase (PtdInsP5K) we were interested in, and our results appeared to contradict previously published data. I dove into the literature and discovered one study suggesting that some of these effects might be isoform specific. When we tested several isoforms of PtdInsP5K, we found that membrane processes were differentially regulated by each isoform. This eureka moment not only resolved the apparent contradiction between our results and prior work, but opened up a new understanding of how specificity is achieved within phosphoinositide 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 and relevant topical focus. In fact, the paper that inspired the turning point for our project was a 2011 publication of the Journal of Cell Science (Calloway et al., 2011).

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Yes, during my training as a researcher I have met great scientists. They taught me how important it is to find a balance between being a 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 a healthy sense of community and family.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

Since I was a child I have been curious about nature and how it works. My career in science allows me to ask questions and pursue their answers, each day learning something new and understanding better how things work. When I took my first academic stay out of Mexico as a graduate student, I met individuals with the same passion and drive for science and realized this could be my career.

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

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

Who are your role models in science? Why?

As I mentioned above, Bertil Hille and Jill Jensen are my role models. Both share a strong criticism for each experiment that teaches me to increase the quality of my experiments every day. At the same time, they are open-minded and keep up-to-date, both great qualities to do science. Finally, Jill Jensen has been my role model to be a great scientist and mother.

What's next for you?

I am continuing my training with a second postdoctoral stay and hope to open my own laboratory in Mexico in a few years.

Tell us something interesting about yourself that wouldn't be on your CV

I also love archaeology, and have attended seminars and conferences about Mexican archaeology. My dream is to collaborate with archeologists on research projects.

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

References

Calloway
,
N.
,
Owens
,
T.
,
Corwith
,
K.
,
Rodgers
,
W.
,
Holowka
,
D.
and
Baird
,
B.
(
2011
).
Stimulated association of STIM1 and Orai1 is regulated by the balance of PtdIns(4,5)P2 between distinct membrane pools
.
J. Cell Sci.
124
,
2602
2610
.
de la Cruz
,
L.
,
Traynor-Kaplan
,
A.
,
Vivas
,
O.
,
Hille
,
B.
and
Jensen
,
J. B.
(
2020
).
Plasma membrane processes are differentially regulated by type I phosphatidylinositol phosphate 5-kinases and RASSF4
.
J. Cell Sci.
133
,
jcs233254
.