CASK
Peripheral plasma membrane protein CASK (EC 2.7.11.1) (hCASK) (Calcium/calmodulin-dependent serine protein kinase) (Protein lin-2 homolog) [LIN2]
Publications[править]
The present study aimed to reveal aging-related changes in the skeletal muscle of SD rats by comparing transcriptome analysis, integrated with muscle physiological parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats aged 6 months were set as the young group (YG). After 6 weeks of feeding, the body mass, grip strength, and gastrocnemius muscle mass were determined, and the differentially expressed genes were analyzed by transcriptome sequencing, followed by GO enrichment analysis and KEGG analysis. The results showed that the muscle index and the relative grip strength were lower in OG rats than YG rats. The expressions of AMPK, UCP3, IGF-1, several ion channel associated genes and collagen family genes were down-regulated in OG rats. MGMT, one of the strength determining genes and CHRNa1, a subunit of the acetylcholine receptor were up-regulated in OG rats. The present results supply the global transcriptomic information involved in aging related skeletal muscle dysfunction in rats. The reduced expressions of AMPK, IGF-1, and CASK can explain the losses of muscle mass and function in the aged rats. In addition, the up-regulation of MGMT and CHRNa1 also contribute to muscle wasting and weakness during aging.
MeSH Terms
- Aging
- Animals
- Male
- Muscle Proteins
- Muscle, Skeletal
- Rats
- Rats, Sprague-Dawley
- Transcriptome
Keywords
- Gene expression
- Grip strength
- RNA-Seq technology
- Sarcopenia
Neurexins (NRXNs) are presynaptic terminal proteins and candidate neurodevelopmental disorder susceptibility genes; mutations presumably upset synaptic stabilization and function. However, analysis of human cortical tissue samples by RNAseq and quantitative real-time PCR at 8-12 postconceptional weeks, prior to extensive synapse formation, showed expression of all three NRXNs as well as several potential binding partners. However, the levels of expression were not identical; [[NRXN1]] increased with age and [[NRXN2]] levels were consistently higher than for [[NRXN3]]. Immunohistochemistry for each NRXN also revealed different expression patterns at this stage of development. [[NRXN1]] and [[NRXN3]] immunoreactivity was generally strongest in the cortical plate and increased in the ventricular zone with age, but was weak in the synaptogenic presubplate (pSP) and marginal zone. On the other hand, [[NRXN2]] colocalized with synaptophysin in neurites of the pSP, but especially with GAP43 and CASK in growing axons of the intermediate zone. Alternative splicing modifies the role of NRXNs and we found evidence by RNAseq for exon skipping at splice site 4 and concomitant expression of KHDBRS proteins which control this splicing. [[NRXN2]] may play a part in early cortical synaptogenesis, but NRXNs could have diverse roles in development including axon guidance, and intercellular communication between proliferating cells and/or migrating neurons.
MeSH Terms
- Aging
- Calcium-Binding Proteins
- Cell Adhesion Molecules, Neuronal
- Cerebral Cortex
- Embryonic Development
- Female
- Gene Expression Regulation, Developmental
- Humans
- Infant
- Male
- Nerve Tissue Proteins
- Neural Cell Adhesion Molecules
- Neurogenesis
- Tissue Distribution
Keywords
- cortical development
- neurexins
- neurodevelopmental disorders
- subplate
The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog. The syndecan-CASK interaction may be involved in intercellular signaling and/or cell adhesion. Here we show that syndecan-1 to syndecan-4 have distinctive mRNA distributions in adult rat brain by in situ hybridization, with syndecan-2 and -3 being the major syndecans expressed in neurons of the forebrain. At the protein level, syndecan-2 and -3 are differentially localized within neurons; syndecan-3 is concentrated in axons, whereas syndecan-2 is localized in synapses. The synaptic accumulation of syndecan-2 occurs late in synapse development. CASK is a cytoplasmic-binding partner for syndecans, and its subcellular distribution changes strikingly during development, shifting from a primarily axonal distribution in the first 2 postnatal weeks to a somatodendritic distribution in adult brain. This change in CASK distribution correlates temporally and spatially with the expression patterns of syndecan-3 and -2, consistent with the association of both of these syndecans with CASK in vivo. In support of this, we were able to coimmunoprecipitate a complex of CASK and syndecan-3 from brain extracts. Our results indicate that specific syndecans are differentially expressed in various cell types of the brain and are targeted to distinct subcellular compartments in neurons, where they may serve specialized functions. Moreover, CASK is appropriately expressed and localized to interact with both syndecan-2 and -3 in different compartments of the neuron throughout postnatal development.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Brain
- COS Cells
- Embryonic and Fetal Development
- Gene Expression Regulation, Developmental
- Heparan Sulfate Proteoglycans
- Immunohistochemistry
- Membrane Glycoproteins
- Molecular Sequence Data
- Neurons
- Proteoglycans
- RNA, Messenger
- Rats
- Recombinant Proteins
- Sequence Alignment
- Sequence Homology, Amino Acid
- Subcellular Fractions
- Synapses
- Syndecan-1
- Syndecan-2
- Syndecan-3
- Syndecan-4
- Syndecans
- Transcription, Genetic
- Transfection