Journal Club: Physiology, Developmental & Evolutionary Biology, Immunology and Microbiology

Thursday, May 14, 2015

PHYSIOLOGY: Genetic and functional characterization of clonally derived adult human brown adipocytes. Shinoda, K., et al. (Kajimura, S.). Nat Med. 2015. 21(4):389-394.

Not all fat cells are created equal. Unlike white adipose tissue, which specializes in energy storage, brown adipose tissue, which is much less abundant, is specialized for producing heat. Although first identified in other mammals, brown adipose tissue is present in adult humans as well.

Scarce and only recently discovered, human brown adipocytes remain poorly understood. This paper from the Kajimura lab provides major new insights into the molecular details of these cells.

Using single-cell analysis of human brown adipocytes, which express UCP1, they identified a subset of cells that appear to be beige adipocytes -- that is, cells that can differentiate into actively thermogenic brown adipocytes. They also found genes that are highly enriched in brown adipocytes, including KCNK3 and MTUS1, both of which they show to be necessary for thermogenesis.

DEVELOPMENTAL and EVOLUTIONARY BIOLOGY: Continuously growing rodent molars result from a predictable quantitative evolutionary change over 50 million years. Tapaltsvan, V., et al. (Klein, O.D.). Cell Rep. 2015. Epub ahead of print.

Mice kept in captivity must be given access to hard food or other substances to chew, to allow wearing of their continuously growing incisors, which are characteristic of rodents.

Many rodents also have continuously growing molars, which rely on proliferation and differentiation of dental stem cells throughout life.

Tapaltsvan and colleagues have taken advantage of the ability of extensive fossil records to study the evolution of molars in rodents. They observed that although 50 million years ago rodents all had short molars, over time many rodents evolved every taller molars and then continuously growing molars.

They used a Markov model to simulate the observed changes in molar height. They found that the evolution of continously growing molars--that is, the evolution of maintained dental stem cell activity throughout adulthood--appears to be predictable rather than the result of a one-time fluke. 

IMMUNOLOGY: The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Onizawa, M., et al. (Ma, A.). Nat Immunol. 2015. Epub ahead of print.

A few proteins have a simple, easily defined function. A20 is not such a protein. Previous research has shown it to be a ubiquitin-modifying enzyme essential for preventing excessive inflammation. Although several mechanisms for how it acts to regulate inflammation have been found, gaps remained.

In this paper, the authors describe a role for A20 in necroptosis, a form of cell death that is regulated but inflammation-promoting (unlike apoptosis). They found that A20-deficient cells were more susceptible to necroptosis.

Additional experiments revealed this effect to be dependent on RIPK3. It appears that A20 limits ubiquitination of RIPK3, thereby controlling the formation of RIPK1-RIPK3 complexes that promote necroptosis.

MICROBIOLOGY: Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome. O’Donoghue, A.J., et al. (Bennett, R.J.). PNAS. 2015. Epub ahead of print.

In recent years, North American bat populations have been devastated by white-nose syndrome, a disease caused by the fungus Pseudogymnoascus destructans, which grows well at low temperatures and strikes hibernating bats.

In this paper, resulting from a collaboration between researchers at UCSF and Brown, a pathogenic enzyme produced by this pathogenic fungus is described. They found a collagen-degrading serine peptidase, which they called destructin-1, is secreted by this fungus.

Due to limited abilities to manipulate this fungus, the researchers used a novel approach to identify and find the substrates of secreted enzymes, leading to this discovery. They developed an inhibitor of destructin-1, which they showed worked in vitro, and propose that targeting this enzyme might allow treatment of white-nose syndrome.