March 20, 2009

Aliquots — research highlights from VMC laboratories

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:


A bend in the nuclear pore

Nuclear pores serve as passageways for the transport of molecules into and out of a cell’s nucleus. Pores are formed by the fusion of inner and outer membrane of the nuclear envelope, but the mechanics of pore formation remain unclear.

In the March 9 Journal of Cell Biology, Susan Wente, Ph.D., and colleagues identify two proteins – Yop1 and Rtn1 – that aid in pore construction. The researchers found that deleting both genes from yeast cells produced errors in the position, structure and function of nuclear pores in yeast cells. Additionally, blocking the vertebrate version of Rtn1 – using frog egg extracts – with an antibody also disrupted pore formation.

Since these proteins were previously known to bend the membrane of the endoplasmic reticulum – a network of membranes that processes and transports proteins – into tubes, the findings suggest that these proteins might help stabilize the curvature of the nuclear membrane required for pore formation.

Melissa Marino


Soy foods offer cancer protection

Colorectal cancer incidence is lower in Asian countries than in the West. While dietary factors, like soy intake, might contribute to this lower risk, previous epidemiological links between these factors have been limited and inconsistent.



Gong Yang, M.D., MPH, and colleagues investigated this link in 68,412 healthy Asian women (ages 40 to 70) participating in the Shanghai Women’s Health Study. The investigators collected comprehensive dietary information – including soy intake – at baseline and during a follow-up period of about six years. During the study period, 321 cases of colorectal cancer were diagnosed. The researchers found risk of colorectal cancer decreased with increasing soy intake, primarily in postmenopausal women. Risk decreased more than 30 percent in women with the highest soy intake levels.

The results, published in the Feb. 1 American Journal of Clinical Nutrition, suggest that soy food intake may reduce risk of colorectal cancer and may help explain why colorectal cancer incidence is much lower in Asian countries than in the West.

Melissa Marino


Bone-building compounds

The bone morphogenetic protein BMP-2 is an important growth factor for bone formation, and age-related loss of its activity may be one of the molecular mechanisms involved in the development of osteoporosis.

To discover compounds that stimulate bone formation, Gregory Mundy, M.D., and colleagues developed a cell-based screening assay based on BMP-2 gene expression.

Using this screening tool, the researchers have now identified microtubule assembly inhibitors – compounds that disrupt the dynamics of the cell’s internal scaffolding – as stimulators of BMP-2 expression. They report in the March Molecular and Cellular Biology that microtubule inhibitors potently stimulate bone formation in mice when administered locally or systemically.

They also investigated the molecular mechanisms underlying this effect and propose a model in which microtubule inhibition increases the concentration and activity of the signaling protein Gli2, which in turn enhances BMP-2 expression. Microtubule inhibitors represent a new lead in drug discovery for bone-building therapeutics.

Leigh MacMillan


How mutations spark epilepsy

Mutations in GABA-A receptors – the major inhibitory receptors in the brain – are associated with some inherited forms of epilepsy. Jing-Qiong Kang, M.D., Ph.D., and colleagues are studying the functional consequences of GABA-A receptor mutations to understand the molecular pathways of epilepsy development.



The researchers report in the March 4 Journal of Neuroscience that a particular mutation in the gamma-2 subunit of the GABA-A receptor results in production of a mutant gamma-2 protein that has an adverse effect on wild-type GABA-A receptors. The mutant gamma-2 subunit, which is associated with a form of epilepsy characterized by febrile seizures, reduces the assembly and surface expression of GABA-A receptors, likely by joining with wild-type subunits and targeting them for endoplasmic reticulum associated degradation (ERAD).

In another paper in the same journal issue, the investigators demonstrate that two molecular pathways – nonsense mediated decay (NMD) and ERAD – contribute to an inherited epilepsy associated with a particular GABA-A alpha subunit mutation. The findings could offer new directions for targeted epilepsy therapies.

Leigh MacMillan

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012