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Phosphorylation of the Bruchpilot N-terminus in Drosophila unlocks axonal transport of active zone building blocks.

Driller, Jan H. and Lützkendorf, Janine and Depner, Herald and Siebert, Matthias and Kuropka, Benno and Weise, Christoph and Piao, Chengji and Petzoldt, Astrig G. and Lehmann, Martin and Stelzl, Ulrich and Zahedi, René and Sickmann, Albert and Freund, Christian and Sigrist, Stephan J and Wahl, Markus C. – 2019

Protein scaffolds at presynaptic active zone membranes control information transfer at synapses. For scaffold biogenesis and maintenance, scaffold components must be safely transported along axons. A spectrum of kinases has been suggested to control transport of scaffold components, but direct kinase-substrate relationships and operational principles steering phosphorylation-dependent active zone protein transport are presently unknown. Here, we show that extensive phosphorylation of a 150-residue unstructured region at the N-terminus of the highly elongated Bruchpilot (BRP) active zone protein is crucial for ordered active zone precursor transport in Drosophila Point mutations that block SRPK79D kinase-mediated phosphorylation of the BRP N-terminus interfered with axonal transport, leading to BRP-positive axonal aggregates that also contain additional active zone scaffold proteins. Axonal aggregates formed only in the presence of non-phosphorylatable BRP isoforms containing the SRPK79D-targeted N-terminal stretch. We assume that specific active zone proteins are pre-assembled in transport packages and are thus co-transported as functional scaffold building blocks. Our results suggest that transient post-translational modification of a discrete unstructured domain of the master scaffold component BRP blocks oligomerization of these building blocks during their long-range transport.

Title
Phosphorylation_Driller
Author
Driller, Jan H. and Lützkendorf, Janine and Depner, Herald and Siebert, Matthias and Kuropka, Benno and Weise, Christoph and Piao, Chengji and Petzoldt, Astrig G. and Lehmann, Martin and Stelzl, Ulrich and Zahedi, René and Sickmann, Albert and Freund, Christian and Sigrist, Stephan J and Wahl, Markus C.
Date
2019-03-18
Identifier
10.1242/jcs.225151
Source(s)
Appeared in
Journal of Cell Science - Volume 132, Issue 6
Type
Text