Yale Bulletin and Calendar

March 24, 2006|Volume 34, Number 23

Researchers identify the function
of protein in nerve cell growth

Researchers at Yale have shed new light on the mechanism of nerve cell growth by identifying novel functions for a molecular "motor" protein, myosin-II, according to an article in the March issue of Nature Cell Biology.

As nerve cells develop or attempt to recover after damage, they put forth growth cones, highly flexible extensions that act as environmental sensors. Growth cones use the information they gather to direct the advance of the nerve cells, and it has long been known that such advance depends on the coordinated assembly of actin filament networks.

This study implicates the molecular motor called myosin II as a key part of the process of recycling the actin networks, and ultimately sensing and directing nerve growth.

Proteins in the myosin family function as molecular motors; the most familiar myosins power contraction in heart and skeletal muscles. Myosin II motors are involved in functions such as directed cell movement, cell division and wound closure. While skeletal myosins have been studied in detail, non-muscle myosins are just beginning to be understood, and this work by the Yale team identifies a new role for them.

The researchers -- led by Paul Forscher, professor of molecular, cellular and developmental biology -- used a technique called fluorescent speckle microscopy, or FSM, that let them directly see actin filament assembly, disassembly and movement in living cells. They used FSM to monitor actin dynamics in nerve cells treated with a new drug called blebbistatin, which relaxes non-muscle myosin II and effectively blocks processes such as cell division.

"Past research has focused on how actin structures are assembled at the leading edges of motile cells," says Forscher. "Instead, this paper investigates turnover or recycling of the actin networks. As the complement to actin network assembly, recycling is necessary to prevent actin buildup that could actually impede neuronal advance."

Forscher likens actin networks in the growth cone to a molecular treadmill that is constantly being assembled at the leading edge and moved rearward, powered by a myosin II motor located at its back end. But the networks making up this actin treadmill are constantly being recycled at the back end, and actin molecules are freed to complete a "virtual belt" cycle and be used again.

"Surprisingly, growth cones of nerve cells rapidly doubled in width when myosin II was blocked by blebbistatin," says Forscher. "FSM see that this was caused by inefficient recycling of actin filaments at the back end of the actin network treadmill."

Recycling of actin bundles at the ends of structures called filopodia was most strongly affected. This is important because filopodia are thought to play a key sensory role in growth cone guidance -- suggesting actin filament recycling and signaling may be intimately related.

The team is now investigating the implications of these findings for control of nerve growth, with particular interest in repair of spinal cord nerves after injury.

Yale co-authors on the paper are Nelson A. Medeiros and Dylan T. Burnett. Support for the project was from a National Institutes of Health grant and the Nikon Partners-in-Research Program.

-- By Janet Rettig Emanuel

T H I SW E E K ' SS T O R I E S

Shauna King named vice president for finance and administration

Project will aid Ethiopia's HIV/AIDS patients

Team finds gene that can prevent kidney stones

Budding scientists

Range of global health issues will be explored . . .

Researchers identify the function of protein in nerve cell growth

Event will examine redevelopment of the waterfront in three cities

'Mabou Mines Dollhouse' is an untraditional rendition of classic play

Project to enhance collection related to colonial India

Former Yale Daily News editor to pursue journalism work in Asia . . .

Civil rights in American law to be addressed in talk

Castle Lectures will explore the costs and advantages . . .

In Memoriam: George F. Mahl

Dwight Hall hosts an online and silent auction to raise funds . . .

PIER seminar aims to link ancient and modern history of Iran

Yale Books in Brief

Campus Notes

Correction