Molecular Motors And Brakes Work Together In Cells

“Up until now motors and brakes were studied separately from microtubules,” says senior author Phong Tran, PhD, Assistant Professor of Cell and Developmental Biology. “This study lets us have a more complete picture.”

Microtubules are structures that help give shape to many types of cells, form the spindle – a structure important in cell division – and act as a railroad, of sorts, upon which molecular motors move protein packages for waste removal and nerve transmission.

In the Cell study, the investigators, working with fission yeast cells, showed that stable end-to-end arrays of microtubules can be achieved by a balance between the sliding by a molecular motor called klp2p and the braking of a microtubule-associated protein (MAP) called ase1p. Specifically, they showed that a preexisting “mother” microtubule acts as a platform on which a new microtubule can be formed. The new “daughter” microtubule grows and moves along the mother microtubule. In time, the daughter grows beyond the end of the mother to ultimately produce two microtubules, connected by the cross-linking MAP ase1p.

“Imagine that the daughter microtubule is a short train on the track of the mother microtubule,” explains Tran. “The molecular motor is the train’s engine, but the problem is that the cargo – the molecular brakes – gets longer, slowing down the daughter train. But when the train gets to the end of the track it remains attached to the end of mother microtubule. At the tail end, it stops moving and that defines the region of overlap. Our work shows that the cell can make microtubule structures of defined lengths stable by coordinating the sliding of the motors and the slowing of the brakes.”

If microtubule-based structures are not formed properly because of failures in brakes or motors, such basic functions as cell division and cell transport can go awry, with such diseases as cancer and dementia possibly resulting. “For the first time we have shown how MAPs and motors work together in a mechanistic way,” says Tran. “This is important and it will make other people who study microtubules rethink how they study the cell.”

Co-authors are Marcel E. Jansen, Isabelle Loïodice, and Chaunhai Fu, all from Penn, and Rose Loughlin, Damian Brunner, and François J. Nédélec from the European Molecular Biology Laboratory, Heidelberg, Germany. The research was sponsored by the National Institutes of Health.

PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals, all of which have received numerous national patient-care honors [Hospital of the University of Pennsylvania; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.