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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 - SorCS2 is required for BDNF-dependent plasticity in the hippocampus

- Research news

SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75NTR, required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation. Although the interaction with p75NTR was static, SorCS2 bound to TrkB in an activity-dependent manner to facilitate its translocation to postsynaptic densities for synaptic tagging and maintenance of synaptic potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2-/- mice displayed impaired formation of long-term memory, increased risk taking and stimulus seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75NTR and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.