Origin and evolution of synaptic proteins
The goal of our laboratory is to reconstruct the origin and evolution of synaptic proteins. We use choanoflagellates, the closest living relatives of animals, sponges, basal animals with no synapses and neurons, and ctenophores, basal animals with synapses and neurons, as model organisms. We aim to understand when the proteins required for synaptic activity first evolved, how they functioned at a molecular level and which combinations of synaptic proteins resulted in the origin of the synapse.
Neurons, synapses, and the proteins required for their function are critical to the biology and behavior of animals but little is known about how they first evolved. In neurons, the transmission of chemical signals (called neurotransmitters) from the presynapse to the postsynapse requires distinct sets of pre- and postsynaptic protein networks. Understanding when the proteins required for synaptic activity first evolved and how they functioned in the first animals promises to illuminate evolutionary processes underlying the origin of neurons. We are particularly interested in:
- The origin and functional evolution of synaptic proteins.
- Co-option of these proteins into ancient synaptic scaffolds.
- Evolution of the first neuron-like cell type in animals.
Our approach is to use a variety of techniques, ranging from comparative genomics, immunofluorescence and electron microscopy, current state-of-the-art biochemical methods to X-ray crystallography to study synaptic protein homologs in choanoflagellates, sponges and ctenophores. Our primary model organisms are the choanoflagellates Salpingoeca rosetta and Monosiga brevicollis, the sponge Sycon ciliatum and the ctenophore Pleurobrachia pileus. Through our work we will be able to reconstruct the evolutionary history of these proteins and understand the evolution of the first synapses and neurons.
Morey C, Kienle CN, Klöpper TH, Burkhardt P and Fasshauer D (2017) Evidence for a conserved inhibitory binding mode between the membrane fusion assembly factors Munc18 and syntaxin in animals. JBC (in press).
Burkhardt P and Sprecher SG (2017) Evolutionary origin of synapses and neurons – Bridging the gap. BioEssays (39) 1700024.
Hoffmeyer TT and Burkhardt P (2016) Choanoflagellate models – Monosiga brevicollis and Salpingoeca rosetta. Curr. Opin. Gen. & Dev. (39) 42-47.
Bhattacharyya M*, Stratton MM*, Going CC*, McSpadden E, Huang Y, Susa AC, Elleman A, Cao YM, Pappireddi N, Burkhardt P, Gee C, Barros T, Schulman H, Williams ER and Kuriyan J. Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II. (2016) eLife 10.7554/eLife.13405 (*joint 1st author).
Burkhardt P (2015) The origin and evolution of synaptic proteins – choanoflagellates lead the way. (2015) J Exp Biol (218), 506-514.
Burkhardt P, Gronborg M, McDonald K, Tulur T, Wang Q and King N (2014) Evolutionary insights into premetazoan functions of the neuronal protein Homer. Mol. Biol. Evol. (31), 2342–2355.
Demircioglu FD, Burkhardt P, Fasshauer D (2014) The SM protein Sly1 accelerates assembly of the ER-Golgi SNARE complex. PNAS (111), 13828-13833.
Sebe-Pedros A*, Burkhardt P*, Sánchez-Pons N, Fairclough SR, Lang F, King N and Ruiz- Trillo I (2013) Insights into the origin of metazoan filopodia and microvilli. Mol. Biol. Evol. 30 (9): 2013-2023 (*joint 1st author).
- Cover Image and fast track publication
Colbert KN, Hattendorf DA, Weiss TM, Burkhardt P, Fasshauer D and Weis WI (2013) Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation. PNAS 110 (31): 12637-42.
Meijer M*, Burkhardt P*, de Wit H, Toonen RF, Fasshauer D and Verhage M (2012) Munc18-1 mutations that abolish SNARE-complex binding support normal synaptic transmission. EMBO Journal (31): 2156-2168 (*joint 1st author).
- Recommended by the Faculty of 1000
Burkhardt P, Stegmann CM, Cooper B, Kloepper TH, Imig C, Varoqueaux F, Wahl MC and Fasshauer D (2011) Primordial neurosecretory apparatus identified in the choanoflagellate Monosiga brevicollis. PNAS, 108 (37): 15264-15269.
- See news story in New Scientist: Your brain chemistry existed before animals did.
Burkhardt P, Hattendorf DA, Weis WI, Fasshauer D (2008) Munc18 controls SNARE assembly through its interaction with the syntaxin N-peptide. EMBO Journal (27): 923-933.
- Recommended by the Faculty of 1000