Journal Club: Immunology, Cancer Biology, Neuroscience, and Cell Biology

Graduate Division

IMMUNOLOGY: Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T-cells. Zhang, Y.; Chen, Y.C.; Krummel, M.F.; Rosen, S.D. Journal of Immunology.  September 7. [Epub ahead of print]

In order for a naïve T-cell to become activated and affect the adaptive immune response, it must move from the blood into a lymph node so that it can interact with an activating dendritic cell. While it is well understood that T-cells move from blood to lymph nodes at points of high endothelial venules (HEVs), many questions remain concerning the process by which the T-cell moves out of the blood vessel and into the lymph node (called “transendothelial migration”). In this paper, researchers tried to ascertain a means by which the T-cell knows to begin transendothelial migration at the location of the HEV. They identified ATX, an enzyme that creates lysophosphatidic acid (a lipid that can influence cellular behavior and has been shown to be involved in transendothelial migration) and found it released by the HEV into the blood. They showed that T-cells have a receptor on their leading edge for ATX that promotes their transendothelial migration and therefore their movement from the blood to the lymph node.

CANCER BIOLOGY: Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis. To, M.D.; Rosario, R.D.; Westcott, P.M.; Banta, K.L.; Balmain, A. Oncogene. September 3. [Epub ahead of print]

Ras genes are a family of small GTPases involved in transducing cellular signals for a number of processes, including cell division, cell growth, and cell adhesion/motility. As such, many cancerous cells that have alterations to cell division, growth, or adhesion/motility are found to have mutations in one or more Ras genes. In many cancers where one Ras gene allele is mutated, the other Ras allele has also been deleted, which has led researchers to believe that one <pls check edit with author>functional allele of a Ras gene is sufficient to limit the development of cancer via the mutated Ras allele. In this paper, researchers created combinations of multiple mutated Ras genes and compared the ability of different combinations to prevent the development of lung and skin cancers. They found the greatest inhibition of cancerous traits occurred when they supplemented the cancerous allele with a healthy allele of the same Ras gene, although there were also some combinations of multiple alleles that provided partial protection.

NEUROSCIENCE: Ectopic uterine tissue as a chronic pain generator. Alvarez, Pet al., (Levine). Neuroscience. August 23. [Epub ahead of print]

Endometriosis is a gynecological disease of variable severity that is caused by endometrial tissue that forms outside the uterus. It causes pain during menstruation and can eventually lead to infertility in some cases, due to extensive abdominal scarring where the endometrial tissue is present. Much of the disease formation, treatment, and prognosis remains a mystery, and the cause of endometrial pain is poorly understood, since even mild cases of endometriosis are sometimes characterized by debilitating pain during menstruation. Here, researchers investigated the cause of endometrial pain in the hopes of developing better treatments. To help learn more, they generated a model of endometriosis in rats by implanting endometrial tissue into the abdominal cavity. Within two weeks, the rats had developed an endometriosis-like condition characterized by pain and cystic endometrial tissue outside the uterus that was treatable with progesterone or leuprolide.

CELL BIOLOGY: Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG. Foraker, A.B. et al., (Brodsky). Journal of Cell Biology. 198(4):591-605.

Clathrin is probably best known for its role in assembling coated pits in the cell membrane to allow for endocytosis; however, the presence of clathrin is also required during mitosis for the cell to properly assemble and move the mitotic spindle along which the cell divides. Depletion of clathrin via RNAi has demonstrated this, but has also suggested that additional proteins may be involved in cell division through interactions with clathrin. Here, researchers wanted to isolate the function of clathrin by selectively inactivating it at different phases of mitosis. They found that inactivation of clathrin in the S phase caused a drop in centrosome-associated clathrin and ch-TOG in metaphase, which was accompanied by fragmentation of the centrosomes. Furthermore, the total amount of ch-TOG was reduced in the cell. This reflects clathrin’s role in centrosome integrity through its stabilization of ch-TOG.