Martin Balastik Group

Laboratory of Molecular Neurobiology

Institute of Physiology, CAS
DIGS-BB Partner Cluster

Martin Balastik

During development of human brain 86 billion neurons form over 1014 connections (synapses). Precision of these connections is critical for the brain function and changes of brain connectivity have been associated with several neurodevelopmental disorders as autism, schizophrenia or epilepsy. Neuron connections are generated through processes of axon/dendrite guidance, synapse formation and refinement. Their growth is controlled at the extracellular level by gradients of attractive or repulsive guidance cues, which are translated into appropriate changes of cytoskeletal dynamics within the growing neurons.

Our laboratory is interested in the regulation of development of the brain connectivity. We characterize the molecular mechanisms responsible for the precise translation of the extrinsic guidance signals into changes of microtubule (MT) dynamics, enabling a fine-tuned response of every growing neuron projection and allowing it to reach its correct cellular target. We focus on the role of microtubule-associated proteins (MAPs) and tubulin post-translational modifications (PTMs) and utilize a combination of in vitro MT systems and primary neuron cultures to characterize the molecular and biological functions of various MAP isoforms and tubulin PTMs, as well as their mutual regulation. Furthermore, we generate and analyze new germinal (knock-out) and somatic (in utero electroporation) mouse mutants and analyze how different splice variants of MAPs in combination with tubulin PTMs affect neuron polarization, migration and cortical development in embryonic development. To characterize their role in adult mice, we use life intravital microscopy of cortical pyramidal neurons through cranial windows. The combination of model systems and techniques provides a detail information about the molecular function and developmental role of MAP isoforms and tubulin PTMs as well as their relevance for pathogenesis of neurodevelopmental disorders.

Phosphorylation
Phosphorylation of the MT-associated protein CRMP2 destabilizes MTs upon stimulation of axonal growth cones by a repulsive guidance cue (model, upper central panel). Tracking of GFP-labeled cortical pyramidal neuron projections using in utero electroporation (lower central panel). Analysis of DiI-labeled pyramidal neuron dendritic trees and dendritic spines and their 3D modeling (right panel). Growth of the callosal axons into the contralateral cortex as analyzed by the in utero electroporation (upper right panel) and its deregulation caused by CRMP2 deficiency (lower right panel).

FUTURE PROJECTS

  • MAPs in axon growth, guidance and pruning – an isoform-specific role of CRMP (Collapsin response mediator proteins) protein family.
  • Prolyl isomerases in neural development - conformational regulation of CRMPs by prolyl isomerases and its role in neural development.
  • Combinatorial effect of tubulin PTMs and MAPs on the regulation of neuron polarization, migration and pruning in vivo/in vitro.
Contact

Institute of Physiology, Czech Academy of Sciences

Videnska 1083

14000 Prague 4

Czech Republic

CV

since 2014

Group leader at the Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

2012-2013

Principal investigator at the Institute of Molecular Genetics, Prague, Czech Republic

2004 -2011

Postdoc at Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, USA

2003

PhD in Neuroscience, International Max Planck Research School, Göttingen, Germany

Selected publications

Ziak J, Weissova R, Jerabkova K, Janikova M, Maimon R, Petrasek T, Pukajova B, Kleisnerova M, Wang M, Brill MS, Kasparek P, Zhou X, Alvarez-Bolado G, Sedlacek R, Misgeld T, Stuchlik A, Perlson E, Balastik M.
CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling
EMBO REPORTS. 2020; 21(3); e48512

Magiera MM, Bodakuntla S, Ziak J, Lacomme S, Sousa PM, Leboucher S, Hausrat TJ, Bosc C, Andrieux A, Kneussel M, Landry M, Calas A, Balastik M, Janke C.
Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport.
EMBO Journal 2018, 37(23), e100440

Balastik M, Zhou XZ, Alberich-Jorda M, Weissova R, Ziak J, Pazyra-Murphy MF, Cosker KE, Machonova O, Kozmikova I, Chen CH, Pastorino L, Asara JM, Cole A, Sutherland C, Segal RA, Lu KP.
Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons
Cell Reports. 2015, 13(4), 812-828

Min SH, Lau AW, Lee TH, Inuzuka H, Wei S, Huang P, Shaik S, Lee DY, Finn G, Balastik M, Chen CH, Luo M, Tron AE, Decaprio JA, Zhou XZ, Wei W, Lu KP.
Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase
Mol Cell. 2012 Jun 29;46(6):771-83