Children's rights in pediatrics

The United Nations Convention of Children's Rights (UNCRC) introduced in 1989 has generated a global movement for the protection of children's rights and has brought about a paradigm change in how children are perceived. Pediatric healthcare professionals are interacting with children and therefore with children's rights on a daily basis. However, although at least 18 of the 54 articles are relevant for pediatric practice, there is limited systematic training on how pediatricians can support children's rights in the clinical setting. This article discusses the principles and aims of the UNCRC and proposes a comprehensive checklist of rights vis-à-vis issues that arise in clinical practic

Interaction between GRIP and Liprin-α/SYD2 Is Required for AMPA Receptor Targeting

Interaction with the multi-PDZ protein GRIP is required for the synaptic targeting of AMPA receptors, but the underlying mechanism is unknown. We show that GRIP binds to the liprin-α/SYD2 family of proteins that interact with LAR receptor protein tyrosine phosphatases (LAR-RPTPs) and that are implicated in presynaptic development. In neurons, liprin-α and LAR-RPTP are enriched at synapses and coimmunoprecipitate with GRIP and AMPA receptors. Dominant-negative constructs that interfere with the GRIP-liprin interaction disrupt the surface expression and dendritic clustering of AMPA receptors in cultured neurons. Thus, by mediating the targeting of liprin/GRIP-associated proteins, liprin-α is important for postsynaptic as well as presynaptic maturation

Neurotransmitter release regulated by a MALS–liprin-α presynaptic complex

Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli–CASK–Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-α as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS–CASK–liprin-α complex recruits components of the synaptic release machinery to adhesive proteins of the active zone

Association of the Kinesin Motor KIF1A with the Multimodular Protein Liprin-α

Liprin-alpha/SYD-2 is a multimodular scaffolding protein important for presynaptic differentiation and postsynaptic targeting of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid glutamate receptors. However, the molecular mechanisms underlying these functions remain largely unknown. Here we report that liprin-alpha interacts with the neuron-specific kinesin motor KIF1A. KIF1A colocalizes with liprin-alpha in various subcellular regions of neurons. KIF1A coaccumulates with liprin-alpha in ligated sciatic nerves. KIF1A cofractionates and coimmunopreciptates with liprin-alpha and various liprin-alpha-associated membrane, signaling, and scaffolding proteins including alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors, GRIP/ABP, RIM, GIT1, and beta PIX. These results suggest that liprin-alpha functions as a KIF1A receptor, linking KIF1A to various liprin-alpha-associated proteins for their transport in neurons

Structure, Tissue Distribution and Genomic Organization of the Murine RRM-Type RNA Binding Proteins TIA-1 and TIAR

TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif (RRM)/ribonucleoprotein (RNP) family that have been implicated as effectors of apoptotic cell death. We report the structures of murine TIA-1 and TIAR (mTIA-1 and mTIAR) deduced from cDNA cloning, the mRNA and protein tissue distribution of mTIA-1 and mTIAR, and the exon-intron structures of the mTIA-1 and mTIAR genes. Both mTIA-1 and mTIAR are comprised of three ∼100 amino acid N-terminal RRM domains and a ∼90 amino acid C-terminal auxiliary domain. This subfamily of RRM proteins is evolutionarily well conserved; mTIA-1 and mTIAR are 80% similar to each other, and 96 and 99% similar to hTIA-1 and hTIAR, respectively. The overall exon-intron structures of the mTIA-1 and mTIAR genes are also similar to each other, as well as to the human TIA-1 gene structure. While Northern blot analysis reveals that mTIA-1 and mTIAR mRNAs have a broad tissue distribution, mTIA-1 and mTIAR proteins are predominantly expressed in brain, testis and spleen. At least two isoforms of both mTIA-1 and mTIAR are generated by alternative splicing. Murine TIA-1 isoforms including or lacking the exon 5 encoded sequences are expressed at a ratio of ∼ 1:1, whereas mTIAR isoforms including or lacking the 5′-end of exon 3 sequences are expressed in a ∼ 1:6 ratio. Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of the functional roles of these proteins during mammalian developmen