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Sorting out Polarized Transport in Neurons: Motor Protein Selectivity and Cooperativity

Objective

Neurons are the building blocks of the brain. The ability of neurons to receive, process and transmit information depends on their polarized organization into axons and dendrites. To build such a highly polarized cell, cellular components synthesized in the cell body are differentially transported to either axons or dendrites. Polarized transport is driven by three families of cytoskeletal motor proteins, which can walk in different directions over the actin or microtubule cytoskeleton. Many subfamilies of motor proteins exist, but how each of these motor proteins contributes to selective cargo delivery is unknown.

I have recently developed an approach to probe specific motor activity inside cells, which revealed that many microtubule-based motors selectively target axons. However, the molecular mechanisms behind this remarkable selectivity are unknown. In addition, it is well-established that most cargos are transported by a combination of different motors, but how the activity of different types of motors on the same cargo is integrated has remained unclear.

The aim of this proposal is to understand how motor proteins navigate the neuronal cytoskeleton. We will take a multidisciplinary approach and combine neurobiology, molecular engineering, advanced microscopy, and mathematical modelling to study the origin of motor selectivity as well as the collective activity of dissimilar motor teams. We will employ and expand our unique methodology to: 1) Study how the spatial organization and post-translational modifications of the microtubule cytoskeleton facilitate selective transport. 2) Perform well-controlled intracellular multi-motor assays to understand the functional interplay between different types of motors.

Successful achievement of these objectives will uncover key mechanisms of polarized transport, which will be relevant for understanding transport-associated neurodegenerative diseases.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /social sciences/social and economic geography/transport
  • /natural sciences/biological sciences/neurobiology

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITEIT UTRECHT
Address
Heidelberglaan 8
3584 CS Utrecht
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 500 000
Principal investigator
Lukas Christiaan Kapitein (Dr.)
Administrative Contact
Astrid Haijma (Mrs.)

Beneficiaries (1)

UNIVERSITEIT UTRECHT
Netherlands
EU contribution
€ 1 500 000
Address
Heidelberglaan 8
3584 CS Utrecht
Activity type
Higher or Secondary Education Establishments
Principal investigator
Lukas Christiaan Kapitein (Dr.)
Administrative Contact
Astrid Haijma (Mrs.)