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. Yuan Gao is first author on ‘ PDZD8-mediated lipid transfer at contacts between the ER and late endosomes/lysosomes is required for neurite outgrowth’, published in JCS. Yuan is a PhD Student in the lab of Dr Weike Ji at the School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, investigating inter-organelle interaction.

Yuan Gao

How would you explain the main findings of your paper in lay terms?

The endoplasmic reticulum (ER) and endosomes are the two main organelles in the secretory and endocytic pathways. These two organelles are connected either through vesicular transport or through the formation of membrane contact sites (MCSs) mediated by tether proteins. Many such tether proteins also function as lipid transporters that mediate the transfer of specific membrane lipids between opposing membranes of the two adjacent organelles. Although the ER has been reported to play an important role in endosome trafficking, maturation and division, whether the lipid transfer mediated by lipid transporters at ER–endosome MCSs regulates the endosomal dynamics remains elusive. Here, we investigated the lipid transfer activities of PDZD8, a recently identified tether protein at ER–late endosome/lysosomes (LE/lys) MCSs, and explored the extent to which its cellular functions depended on its lipid transfer activities. In accordance with recent studies, we demonstrate that PDZD8 acts as a tether at ER–LE/lys MCSs. We next followed up more closely on the lipid transfer activities of PDZD8. We discovered that the SMP domain of PDZD8 bound glycerophospholipids and ceramides both in vivo and in vitro, and that the SMP domain could transport these specific lipids between membranes in vitro. Functionally, we showed that the lipid transfer activity of PDZD8 is required for the proper trafficking of LE/lys and for the growth of new projections of developing neurons in response to neuronal growth factors.

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

We encountered many small technical problems throughout the study. For example, there are no commercial anti-PDZD8 antibodies for western blots and immunofluorescence, meaning we sometimes had to get creative with our experiments. To visualize PDZD8, we made a cell line stably expressing PDZD8–GFP driven by a weak promoter. By doing so, we could observe the cellular localization of PDZD8–GFP very clearly, but also avoid the possible artifacts induced by overexpression.

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

The first time I saw the cellular localization of PDZD8–GFP on a confocal microscope. The entire process remains a vivid memory in my mind. I am still puzzled and amazed at the beautiful localization of PDZD8–GFP at the junctions of the ER and LE/lys, as its localization is definitely different from what was shown in 2017!

Why did you choose Journal of Cell Science for your paper?

Journal of Cell Science is a well-respected journal with a broad readership and it publishes novel and high-quality papers in the field of cell biology. I also like the types of articles published in Journal of Cell Science. For these reasons, I chose Journal of Cell Science for my paper.

The dynamics of PDZD8-GFP at ER–LE/lys MCSs. Yellow arrows denote the enrichment of PDZD8–GFP at MCSs. Green, PDZD8–GFP; Magenta, Lamp1–Halo; Cyan, ER-tagRFP. Time is in seconds.

The dynamics of PDZD8-GFP at ER–LE/lys MCSs. Yellow arrows denote the enrichment of PDZD8–GFP at MCSs. Green, PDZD8–GFP; Magenta, Lamp1–Halo; Cyan, ER-tagRFP. Time is in seconds.

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

I am thankful to my current PhD mentor Dr Weike Ji for his guidance. He was very patient, critical and always ready to discuss experimental results and talk about future experiments throughout the project.

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?

When I was pursuing my bachelor's and master's degrees, I experienced scientific research in different fields. Eventually, I fell completely in love with cell biology. The cell biologists and mentors I knew were very supportive and critical people, and I decided to take the next step into cell biology research.

Who are your role models in science? Why?

There is no specific person in my mind. But I think that all my colleagues, lab mates and undergraduate students who are hard-working, self-driven and who think critically are my role models.

What's next for you?

I haven't yet finished my graduate studies. There is still plenty of work to be done.

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

I love reading, and I typically spend around two hours a day reading books (not scientific papers!).

Yuan Gao's contact details: School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. E-mail: [email protected]

Gao
,
Y.
,
Xiong
,
J.
,
Chu
,
Q.-Z.
and
Ji
,
W.-K.
(
2022
).
PDZD8-mediated lipid transfer at contacts between the ER and late endosomes/lysosomes is required for neurite outgrowth
.
J. Cell Sci.
135
,
jcs255026
.