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van der Meer, E.

Publications and source records attributed to van der Meer, E..

2 recordsLinked to original sources

Spatiotemporal proteomics elucidates trafficking and localization of Neuroligins to the axon initial segment plasma membrane

Neuronal development and function rely on precise sorting of membrane proteins to distinct neuronal domains, yet the underlying mechanisms remain incompletely understood. Here, we investigated the trafficking of two highly homologous NLGNs (NLGN1 and 2) which distinctly localize and function at excitatory and inhibitory synapses. By using spatiotemporal proteomics, genetic engineering and microscopy in CNS cultured neurons and organotypic slices, we dissected the itinerary of biosynthetic NLGNs, identifying co-cargoes and sorting routes to dendrites and the AIS. At the AIS, which contains only inhibitory synapses, both NLGN1 and NLGN2 are locally exocytosed. While NLGN2 is stably recruited to axo-axonic synapses by its extracellular domain and modulated by activity, NLGN1 is retrieved by endocytic mechanisms. We propose that biosynthetic NLGNs are co-sorted to the AIS PM where they detect pre-synaptic type. These findings may help to elucidate the role of AIS-localized NLGNs in shaping AIS structural and functional plasticity. HighlightsO_LISpatiotemporal proteomics elucidates interactome of biosynthetic NLGN1 in neurons C_LIO_LINLGN1 and NLGN2 are targeted to the AIS by kinesin-1 C_LIO_LINLGN2, but not NLGN1, is retained at axo-axonic synapses and modulated by activity C_LIO_LINLGN stability at the AIS plasma membrane is determined by the ectodomain C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/733123v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@a45909org.highwire.dtl.DTLVardef@1d171b0org.highwire.dtl.DTLVardef@17f132aorg.highwire.dtl.DTLVardef@1c33a8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Entering the era of conservation genomics: Cost-effective assembly of the African wild dog genome using linked long reads

A high-quality reference genome assembly is a valuable tool for the study of non- model organisms across disciplines. Genomic techniques can provide important insights about past population sizes, local adaptation, and even aid in the development of breeding management plans. This information can be particularly important for fields like conservation genetics, where endangered species require critical and immediate attention. However, funding for genomic-based methods can be sparse for conservation projects, as costs for general species management can consume budgets. Here we report the generation of high-quality reference genomes for the African wild dog (Lycaon pictus) at a low cost, thereby facilitating future studies of this endangered canid. We generated assemblies for three individuals from whole blood samples using the linked-read 10x Genomics Chromium system. The most continuous assembly had a scaffold N50 of 21 Mb, a contig N50 of 83 Kb, and completely reconstructed 95% of conserved mammalian genes as reported by BUSCO v2, indicating a high assembly quality. Thus, we show that 10x Genomics Chromium data can be used to effectively generate high-quality genomes of mammal species from Illumina short-read data of intermediate coverage ([~]25-50x). Interestingly, the African wild dog shows a much higher heterozygosity than other species of conservation concern, possibly as a result of its behavioral ecology. The availability of reference genomes for non-model organisms will facilitate better genetic monitoring of threatened species such as the African wild dog. At the same time, they can help researchers and conservationists to better understand the ecology and adaptability of those species in a changing environment.

genomics↗