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Nykjær Group

Receptor Neurobiology

Research activities are focused towards the functional characterization of a group of type-1 receptors denoted the Vps10p-domain family, or so-called sortlins, that comprises sortilin, SorLA, and SorCS-1, -2, and -3. The receptors are enriched in neurons where they mediate trafficking and signaling of a vast number of ligands such as neurotrophic factors along with their cognate receptors, neurotransmitter receptors, APP, and progranulin. Among many activities, the receptors regulate neuronal cell fate, differentiation, innervation, synaptic plasticity, and learning and memory. Key goals of the Nykjaer lab is to understand their functions in the heathy brain, dissect out their mode of actions, investigate how genetic variation contributes to disease development - in particular of neuropsychiatric disorders and memory impairment -, and to evaluate their potential as drug targets.

Methodologies include transgenic mice and zebrafish, a broad repertoire of molecular, cellular and genetic and viral tools, transcriptomics and (phospho)proteomics, neuroembryology, mouse behavior, electrophysiology and advanced imaging including high-resolution microscopy. In vivo fiber photometry and mesoscale single unit recordings are currently being implemented.

Available projects 

The Nykjær group currently has projects available for Master students and postdocs within the following research areas. 

Functions of the sortilin receptor family in health and disease:

  • Molecular mechanisms underlying memory and psychiatric disorders

Please contact Group Leader Anders Nykjær directly, if interested.

News

Previous news from the research group

News

New publication from Anders Nykjær's group - Sortilin mediates vascular calcification via its recruitment into extracellular vesicles

- Research news

Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2-dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification.