Publications by authors named "H J Kreienkamp"
Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca/calmodulin-dependent protein kinase II.
View Article and Find Full Text PDFNeurodevelopmental disorders (NDDs) represent a large group of disorders with an onset in the neonatal or early childhood period; NDDs include intellectual disability (ID), autism spectrum disorders (ASD), attention deficit hyperactivity disorders (ADHD), seizures, various motor disabilities and abnormal muscle tone. Among the many underlying Mendelian genetic causes for these conditions, genes coding for proteins involved in all aspects of the gene expression pathway, ranging from transcription, splicing, translation to the eventual RNA decay, feature rather prominently. Here we focus on two large families of RNA helicases (DEAD- and DExH-box helicases).
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- The Concise Guide to PHARMACOLOGY 2023/24 offers a summarized overview of approximately 1800 drug targets and around 6000 interactions with 3900 ligands, mostly in a tabular format.
- It focuses on selective pharmacology and includes links to an open access knowledgebase for more detailed drug information.
- The guide divides drug targets into six major categories, providing essential summaries and guidance based on the latest pharmacological data available as of mid-2023, while serving as an official resource by the International Union of Basic and Clinical Pharmacology.
Members of the Shank family of postsynaptic scaffold proteins (Shank1-3) link neurotransmitter receptors to the actin cytoskeleton in dendritic spines through establishing numerous interactions within the postsynaptic density (PSD) of excitatory synapses. Large Shank isoforms carry at their N-termini a highly conserved domain termed the Shank/ProSAP N-terminal (SPN) domain, followed by a set of Ankyrin repeats. Both domains are involved in an intramolecular interaction which is believed to regulate accessibility for additional interaction partners, such as Ras family G-proteins, αCaMKII, and cytoskeletal proteins.
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- Postsynaptic scaffold proteins like Shank are crucial for forming the density at glutamatergic synapses, and mutations in SHANK genes are linked to disorders like autism and intellectual disability.
- The study identified two new missense mutations in SHANK2 (p.G643R and p.L1800W) that hinder essential functions of Shank proteins, disrupting their ability to bind with other proteins and properly polymerize.
- These mutations negatively impact the targeting of Shank2 in neurons and affect glutamatergic synaptic transmission, indicating that both PDZ- and SAM-domain interactions are vital for the normal development of brain synapses.