The matchmaker that maintains neuronal balance

[Guest guest]

The matchmaker that maintains neuronal balance

http://www.eurekalert.org/pub_releases/2009-03/bcom-tmt031909.php

HOUSTON - (March 25, 2009) – A protein identified by researchers at Baylor

College of Medicine (www.bcm.edu) helps maintain a critical balance between two

types of neurons, preventing motor dysfunction in mammals.

In a report in the current edition of the journal Neuron, Dr. Soo-Kyung Lee

(http://www.bcm.edu/mcb/?PMID=7591), assistant professor of molecular and human

genetics, molecular and cellular biology and neuroscience at BCM, and her

colleagues describe the protein LMO4 as critical in allowing progenitor cells to

choose their fates – between the V2a neurons that are excitatory and the V2b

neurons that are inhibitory. Excitatory neurons encourage the activity of

neurons on which they act. Inhibitory neurons act in an opposite manner.

In previous work, Lee and members of her laboratory identified the

double-barreled or dimerized complex containing the protein Lhx3 that pushes the

progenitor cells to become V2a excitatory neurons. In this paper, she notes the

LMO4 not only forms a complex that binds to DNA and promotes the choice of cell

fate to the V2b inhibitory neurons, it also blocks the path to becoming a V2a

excitatory neuron.

Because LMO4 cannot bind directly to DNA, it plays matchmaker instead, building

a complex of DNA-binding components that allow the cells to choice to become

inhibitory neurons.

" These individual DNA-binding components are present in the neurons, " she said.

" But they do not have the ability to find their DNA partners. LMO4 'glues' these

proteins together and makes them functional. "

She and her colleagues have demonstrated these both in the laboratory and in

mice bred to lack LMO4. Without the protein, the balance becomes tipped in favor

of excitatory neurons, which would result in motor dysfunction.

Others who took part in this research include Kaumudi Joshi, Seunghee Lee, Bora

Lee and Jae W. Lee, all of BCM.

Lee credits graduate student Kaumdi Joshi with much of the laboratory work in

accomplishing this understanding.

###

Funding for this research came from the National Institute of Neurological

Disorders and Stroke, the Pew Scholars in Biomedical Science Program, the March

of Dimes Foundation and the BCM Intellectual and Developmental Disabilities

Research Center.