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Birnbaum, J.

Publications and source records attributed to Birnbaum, J..

3 recordsLinked to original sources

Sex-specific dynamics of activity-dependent regulation of synaptic CaMKII

Similar behavioral outcomes in males and females can mask substantial differences in the mechanisms underlying neuronal function. However, to what extent sex influences the abundance and activity-dependent changes of proteins that govern neuronal plasticity remains poorly understood. Here we investigated sex-specific regulation of calcium/calmodulin-dependent protein kinase II (CaMKII), an evolutionarily conserved regulator of synaptic stability and plasticity in fruit fly Drosophila melanogaster. We find that the steady state levels and activity-driven changes in CaMKII protein differ between female and male at both third instar larval neuromuscular junction (NMJ) and in adult fly mushroom body (MB). These sex-specific differences are downstream of the sex determination pathway, implicating somatic sex identity in the regulation of CaMKII abundance and its activity-dependent dynamics. Despite the differences in CaMKII levels between female and male flies, we observed no impairment of plasticity in either sex. Overall, our findings reveal sex-dependent regulation of both steady-state and activity-dependent levels of a highly conserved neuronal plasticity-associated protein across distinct neuronal contexts and development stages. These results further support the idea that females and males can achieve similar behavioral outcomes through different molecular mechanisms. Growing evidence that sexually dimorphic molecular responses contribute directly to sex differences in vulnerability to stress and disease underscores the importance of identifying these mechanisms and understanding their consequences.

neuroscience↗

Escherichia coli with a 57-codon genetic code

The near-universal genetic code of living organisms uses 64 codons to encode the 20 canonical amino acids in protein synthesis. Here we design and generate a variant of Escherichia coli with a 4 Mb synthetic genome in which we replace every known occurrence of six sense codons and a stop codon with synonymous codons. We thereby recode 105 codons to create an organism with a 57-codon genetic code; this organism - which we name Syn57 - uses 55 codons to encode the 20 canonical amino acids.

synthetic biology↗

The Kelch13 compartment is a hub of highly divergent vesicle trafficking proteins in malaria parasites

Single amino acid changes in the parasite protein Kelch13 (K13) result in reduced susceptibility of P. falciparum parasites to artemisinin and its derivatives (ART). Recent work indicated that K13 and other proteins co-localising with K13 (K13 compartment proteins) are involved in the endocytic uptake of host cell cytosol (HCCU) and that a reduction in HCCU results in ART resistance. HCCU is critical for parasite survival but is poorly understood, with the K13 compartment proteins among the few proteins so far functionally linked to this process. Here we further defined the composition of the K13 compartment by analysing more hits from a previous BioID, showing that MyoF and MCA2 as well as Kelch13 interaction candidate (KIC) 11 and 12 are found at this site. Functional analyses, tests for ART susceptibility as well as comparisons of structural similarities using AlphaFold2 predictions of these and previously identified proteins showed that canonical vesicle trafficking and endocytosis domains were frequent in proteins involved in resistance or endocytosis (or both), comprising one group of K13 compartment proteins. While this strengthened the link of the K13 compartment to endocytosis, many proteins of this group showed unusual domain combinations and large parasite-specific regions, indicating a high level of taxon-specific adaptation of this process. Another group of K13 compartment proteins did not influence endocytosis or ART susceptibility and lacked detectable vesicle trafficking domains. We here identified the first protein of this group that is important for asexual blood stage development and showed that it likely is involved in invasion. Overall, this work identified novel proteins functioning in endocytosis and at the K13 compartment. Together with comparisons of structural predictions it provides a repertoire of functional domains at the K13 compartment that indicate a high level of adaption of endocytosis in malaria parasites.

cell biology↗