Our publications

Check out some of our published work:

 

Zewe J, Wills R, Sangappa S, Goulden B, Hammond G. SAC1 degrades its lipid substrate PtdIns4P in the endoplasmic reticulum to maintain a steep chemical gradient with donor membranes. Elife. elife; 2018;7:e35588. 10.7554/elife.35588

Our first lead author paper from the lab! Check out the full synopsis of the paper and its significance here.

 

Sohn M, Korzeniowski M, Zewe J, Wills R, Hammond G, Humpolickova J, et al. PI(4,5)P2 controls plasma membrane PI4P and PS levels via ORP5/8 recruitment to ER–PM contact sites. J Cell Biol; 2018;jcb.201710095.10.1083/jcb.201710095

ImageJ=1.51n unit=micron finterval=30.07699966430664

Our good friends in the Balla lab published this awesome paper in JCB. They showed a novel “rheostat” that controls PIP2 synthesis at the plasma membrane by controlling the levels of its precursor, PI4P. The rheostat consists of the proteins ORP5 and ORP8: they proteins can remove PI4P from the plasma membrane and dump it at the endoplasmic reticulum – where we showed that SAC1 degrades it. Mira Sohn’s novel finding was that this transfer process requires PIP2 itself. So, when the cell runs short of PIP2, ORP5/8 cannot remove PI4P from the plasma membrane and instead, the PI4P is all used to build PIP2. We helped out in the study by showing that ORP5/8 need PIP2 to localize to the specialized spots on the Plasma membrane – since its lost when we deplete PIP2 (see the picture).

 

Hammond G. DepHining membrane identity. J Cell Biol. 2018 Jan 2;217(1):19–2010.1083/jcb.201711134

Here, Gerry highlighted an awesome paper from the Terebiznik and Botelho labs in Toronto. They showed that a a big identifying marker on the outside of some organelles – the inositol lipids – is actually tightly controlled by a factor identifying the inside of the organelle – its pH. Definitely worth a read!

 

Willett R, Martina J, Zewe J, Wills R, Hammond G, Puertollano R. TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes. Nat Commun; 2017;8(1):1580.10.1038/s41467-017-01871-z

Our colleagues in Rosa Puertollano’s lab at NIH showed found a novel function for the protein TMEM55B: they showed that this protein is integral to strategic positioning the cell’s lysosomes – its waste disposal and recycling centers – by engaging the cells transportation network. We help out a little bit to show that the previously described function for TMEM55B – that it was an enzyme that degrades PIP2 – is actually likely not physiologically relevant, since the enzyme the activity is virtually undetectable.

 

Tóth J, Gulyás G, Tóth D, Balla A, Hammond G, Hunyady L, et al. BRET-monitoring of the dynamic changes of inositol lipid pools in living cells reveals a PKC-dependent PtdIns4P increase upon EGF and M3 receptor activation. Biochimica Et Biophysica Acta – Mol Cell Biology Lipids. sciencedirect; 2016;1861(3):177–87.10.1016/j.bbalip.2015.12.005

In this paper, our colleagues in the Varnai lab in Budapest developed a really cool new Bioluminescence technique with biosensors to quantify inositol lipids in living cells. We helped our by supplying them with improved PI4P biosensors.

 

Hammond, GRV. Does PtdIns(4,5)P2 concentrate so it can multi-task? Biochem Soc Trans.; 2016;44(1):228–33. 10.1042/bst20150211

PrintHere, Gerry discusses the evidence we have so far for how PIP2 is able to co-ordinate so many disparate processes at the cell surface – and why maybe only some of these processes are effected when PIP2 metabolism is messed up in disease.

 

Levin R, Hammond G, Balla T, DeCamilli P, Fairn GD, Grinstein S. Multiphasic dynamics of phosphatidylinositol 4-phosphate during phagocytosis. Molecular biology of the cell. Molecular biology of the cell; 2016;28(1):128–4010.1091/mbc.E16-06-0451

Levine_2016

 

Our good friend Roni Levin in the Grinstein lab in Toronto use some of our probes and tools to study PI4P during phagocytosis – the process whereby immune cells eat waste products and foreign invaders. In this really cool paper, they show that PI4P is a unique regulatory lipid in this process: it is required both for early stages of ingestion, as well at later stages when the internalized body starts to be digested.

 

Xie S, Bahl K, Reinecke JB, Hammond GRV, Naslavsky N, Caplan S. The endocytic recycling compartment maintains cargo segregation acquired upon exit from the sorting endosome. Molecular biology of the cell ; 27(1):108–26. 10.1091/mbc.e15-07-0514

Caplan_2016

This paper looked at the endocytic recycling compartment – essentially a cellular depot where recycled components of the plasma membrane are staged before being returned to the cel surface when needed. Our colleagues in the Caplan lab in Omaha showed that different cargoes are stored in separate compartments in this recycling depot. To do this, they did some really spectacular high-resolution imaging to see molecular cargoes separated (see the picture). We helped out with resolving some of the really high-resolution images to 30-50 nm!

 

Dong W, Zhang X, Liu W, Chen Y, Huang J, Austin E, et al. A conserved polybasic domain mediates plasma membrane targeting of Lgl and its regulation by hypoxia. J Cell Biology; 2015;211(2):273–86. 10.1083/jcb.201503067

Hong_2015

In this paper, we helped out a good friends in the Hong lab (also in the Cell Bio department here at Pitt) to figure out what targeted cell polarity proteins to the cell surface. We used some of our chemical genetic tools to demonstrate that cell polarity proteins depend on the inositol lipids in the plasma membrane to localize there. This shows the  essential role of these lipids in building and maintaining cell polarization in epithelia – a key process that fails in diseases like cancer.