Open AccessPhosphorylation of the Bruchpilot N-terminus unlocks axonal transport of active zone building blocks
Author(s) -
J.H. Driller,
Janine Lützkendorf,
Harald Depner,
Matthias Siebert,
Benno Kuropka,
Christoph Weise,
Chengji Piao,
Astrid G. Petzoldt,
Martin Lehmann,
Ulrich Stelzl,
René P. Zahedi,
Albert Sickmann,
Christian Freund,
Stephan J. Sigrist,
Markus C. Wahl
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.225151
Subject(s) - active zone , scaffold , phosphorylation , scaffold protein , biology , axoplasmic transport , kinase , transport protein , microbiology and biotechnology , synaptic vesicle , biogenesis , biochemistry , membrane , vesicle , signal transduction , engineering , gene , biomedical engineering
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 was 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 BRP/ELKS active zone proteins is crucial for ordered active zone precursor transport. Point mutations that block SRPK79D-kinase-mediated phosphorylation of the BRP/ELKS N-terminus interfered with axonal transport, leading to BRP/ELKS-positive axonal aggregates that also contain additional active zone scaffold proteins. Axonal aggregates formed only in the presence of non-phosphorylatable BRP/ELKS isoforms containing the SRPK79D-targeted N-terminal stretch. We assume that specific active zone proteins are pre-assembled in transport packages and 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 Bruchpilot blocks oligomerization of such building blocks during their long-range transport.