LABORATORY OF SYNAPTOGENESIS

Head: Tomasz J. Prószyński

 

Degrees:

2001-2005 PhD in Biology, Max-Planck  Institute for Cell Biology and Genetics, Dresden, Germany

 

Research trainings:

2006-2012 Post-doctoral training: Harvard University, Joshua Sanes’ Laboratory, USA

2005-2006 Max-Planck Institute for Cell Biology and Genetics, Kai Simons’Laboratory, Dresden, Germany

 

Professional employments:

2013-present Head of Laboratory at the Nencki Institute of Experimental Biology

 

Honors and fellowships:

2007 EMBO Long Term Fellowship

2007 HFSP Long Term Fellowship

Staff: Krzysztof Bernadzki (PhD student), Agata Błażewicz, Marta Gawor, Adrian Kobiela (PhD student), Joanna Krzemień (PhD student), Paula Mazurek (PhD student), Marcin Peziński (PhD student), Anna Protasiuk, Katarzyna Rojek (PhD student)

Research profile:

 

The focus of our laboratory lies within the various aspects of synapse development and cellular communication in the nervous system. We are particularly interested in the developmental remodeling of the neuromuscular junction (NMJ) in the peripheral nervous system. This highly specialized synapse enables transmission of signals from motor neurons to muscle fibers, triggering their contraction. Interestingly there are an estimated 300 types of neuromuscular disorders, and half of these have unknown etiology. This shows how important it is to study the communication between muscle and nerve. Our investigations involve the organization of cytoskeleton at the muscle postsynaptic machinery. We use the state-of-the-art biochemical and molecular approaches to identify novel organizers of these structures, and support our studies with confocal microscopy using the specialized microscopic facility at Nencki Institute. Each project in our laboratory involves conditional knockout mice allowing dissection of the gene’s of interest function, specifically at either the pre- or the postsynaptic compartments. Many proteins involved in the organization of the muscle synaptic machinery are also implicated in synaptic plasticity in the brain. Therefore, the novel NMJ organizers are studied in our laboratory also in the context of neuronal network organization in the brain. This approach led us to the discovery of angiomotin family of proteins that are widely expressed in the brain and regulate neuroskeleton, cellular organization and the social behavior of mutant animals.



Current research activities:

 

We carry out several projects that should allow for a better understanding of the molecu- lar pathways regulated by the newly identified postsynaptic regulators. We are particularly interested  in  signaling  molecules  and  actin  cytoskeletal  organizers  that  regulate remodeling of the NMJ from juvenile, simple, oval plaques into topologically complex structures referred to as “pretzels”. To better understand regulatory processes at the postsynaptic compartments we conduct in vitro experiments on cultured muscle cells able to form post- synaptic specialization. Ongoing projects on the brain are aimed to unravel the molecular functions of Angiomotin family of proteins in neuronal organization. We use several different techniques to evaluate their function in vitro in cultured hippocampal neurons. To study the function in vivo we generated conditional knockout mice with neuron-specific deletion of individual angiomotins. These mice are used to study behavioral abnormalities as  well  as  development  of  the  neuronal  networks. To visualize morphology of individual neurons in vivo we crossed mice to Thy1-GFP transgenic line allowing for sparse labeling of cells or inject brains with low titer GFP-expressing AAV viruses.

 


Selected publications:

 

Α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction. Gingras J, Gawor M, Bernadzki KM, Grady RM, Hallock P, Glass DJ, Sanes JR, Prószyński TJ. J Cell Sci., 2016 Mar 1;129(5):898-911.

 

Podosomes in muscle cells and their role in the remodeling of neuromuscular postsynaptic machinery. Bernadzki KM, Rojek KO, Prószyński TJ. Eur J Cell Biol., 2014 Oct;93(10-12):478-85.

 

Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle. Prószyński TJ, Sanes JR. J Cell Sci, 2013 May 15;126(Pt 10):2225-35.

 

Interaction of α-catulin with dystrobrevin contributes to integrity of dystrophin complex in muscle. Oh HJ, Abraham LS, van Hengel J, Stove C, Proszynski TJ, Gevaert K, DiMario JX, Sanes JR, van Roy F, Kim H. J Biol Chem, 2012 Jun 22;287(26):21717-28.

 

Podosomes are present in a postsynaptic apparatus and participate in its maturation. Prószyński TJ, Gingras J, Valdez G, Krzewski K, Sanes JR. Proc Natl Acad Sci USA. 2009 Oct 27;106(43):18373-8.