Endocrine cells share expression of N-CAM with neurones

The reeent explosive interest in eell adhesion molecules (CAMs) is a direet eonsequence of the fundamental roles they are thought to play during early embryogenesis and tissue formation [1,2]. The most weIl known of them, studied independently under the names of N-CAM [3] (neural-CAM), 02 protein [4] and BSP-2 [5], has been shown to consist in brain of a family of three glyeoproteins of Mr 180000, 140000 and 120000 [6,7] which are implicated in neurone-neurone adhesion by a homophilie binding meehanism [8,9]. While N-CAM was originally considered to be limited to neurones in adult tissues, ultrastruetural immunoeytochemical studies have sinee provided unequivocal evidenee that glial cells, both astrocytes [6,10] and Schwann cells [11], also express N-CAM (see also [12,13]). Apart from a very limited expression by skeletal muscle at the neuromuscular junetion [14], its expression in the adult Correspondence address: O.K. Langley, Unite 44 de I'INSERM, and Centre de Neurochirnie du CNRS, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France has been largely though not exclusively considered to be limited to nervous tissues. N-CAM has been found in eertain eells outside the nervous system (e.g. chromaffin eells in the adrenal medulla [11]) but such eells are derived from the neural crest. Here we extend our previous observations on endocrine eells in the adrenal gland and investigate the possible expression of N-CAM by other endoerine eells whieh have a non-neural origin. The present results indieate a mueh wider distribution of N-CAM in adult tissues than has previously been supposed. N-CAM is shown by immunoeytoehemistry to be expressed by several endoerine eells of non-neural origin. Immunoehemieal data eonfirm the presenee of N-CAM determinants typical of brain in endoerine eells although the relative proportions differ markedly. In addition, in two of the tissues examined a lower molecular mass NCAM positive polypeptide was also detected

Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus

Synaptic NMDA-type glutamate receptors are anchored to the second of three PDZ (PSD-95/Discs large/ZO-1) domains in the postsynaptic density (PSD) protein PSD-95. Here, we report that citron, a protein target for the activated form of the small GTP-binding protein Rho, preferentially binds the third PDZ domain of PSD-95. In GABAergic neurons from the hippocampus, citron forms a complex with PSD-95 and is concentrated at the postsynaptic side of glutamatergic synapses. Citron is expressed only at low levels in glutamatergic neurons in the hippocampus and is not detectable at synapses onto these neurons. In contrast to citron, p135 SynGAP, an abundant synaptic Ras GTPase-activating protein that can bind to all three PDZ domains of PSD-95, and Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) are concentrated postsynaptically at glutamatergic synapses on glutamatergic neurons. CaM kinase II is not expressed and p135 SynGAP is expressed in less than half of hippocampal GABAergic neurons. Segregation of citron into inhibitory neurons does not occur in other brain regions. For example, citron is expressed at high levels in most thalamic neurons, which are primarily glutamatergic and contain CaM kinase II. In several other brain regions, citron is present in a subset of neurons that can be either GABAergic or glutamatergic and can sometimes express CaM kinase II. Thus, in the hippocampus, signal transduction complexes associated with postsynaptic NMDA receptors are different in glutamatergic and GABAergic neurons and are specialized in a way that is specific to the hippocampus

Evidence for a Phosphorylated Form of Calmodulin in Chicken Brain and Muscle

Phosphocalmodulin (PCaM) was identified after analysis of calmodulin (CaM) preparations by two-dimensional gel electrophoresis by using a modified ampholyte system to resolve very acidic proteins. The analysis of CaM prepared by the conventional procedure based upon its heat resistance and acidity as well as the analysis of whole urea extracts from brain showed that PCaM was a major component in this tissue. PCaM was 1 pH unit more acidic than CaM, and its electrophoretic mobility, unlike CaM, was not changed by either calcium or ethylene glycol-bis(β-aminoethyl ether)-N,N-tetraacetic acid. In urea extracts of brain prepared in buffers containing phosphate and sodium fluoride, PCaM was as prominent as CaM; it was partially converted into CaM after elution from the gel and reelectrophoresis. Amino acid analysis of PCaM and CaM purified by two-dimensional gel electrophoresis showed the same composition for the two proteins, including their trimethyllysine content. Incorporation of (^32)P occurred exclusively into the acidic variant when brain slices were incubated with (H_3)(^32(PO_4)); amino acid analysis showed that the phosphate was bound to serine residues. CaM was found also to be phosphorylated in vitro by a phosphorylase kinase preparation from skeletal muscle

A Novel Confidence Induced Class Activation Mapping for MRI Brain Tumor Segmentation

Magnetic resonance imaging (MRI) is a commonly used technique for brain tumor segmentation, which is critical for evaluating patients and planning treatment. To make the labeling process less laborious and dependent on expertise, weakly-supervised semantic segmentation (WSSS) methods using class activation mapping (CAM) have been proposed. However, current CAM-based WSSS methods generate the object localization map using internal neural network information, such as gradient or trainable parameters, which can lead to suboptimal solutions. To address these issues, we propose the confidence-induced CAM (Cfd-CAM), which calculates the weight of each feature map by using the confidence of the target class. Our experiments on two brain tumor datasets show that Cfd-CAM outperforms existing state-of-the-art methods under the same level of supervision. Overall, our proposed Cfd-CAM approach improves the accuracy of brain tumor segmentation and may provide valuable insights for developing better WSSS methods for other medical imaging tasks

Intranuclear differences in calmodulin gene expression in the trigeminal nuclei of the rat brain

The expression patterns of the three CaM genes were quantitatively localized by using in situ hybridization techniques to detect gene-specific [35S]-labeled cRNA probes complementary to the multiple CaM mRNAs in the trigeminal nuclei of the adult rat brain. The three distinct CaM genes were widely expressed throughout the midbrain-brain stem area with moderate intensities. In general, mRNAs transcribed from the CaM III gene were the most abundant, followed by the CaM I and CaM II mRNA populations. Moreover, significant differences in the amounts of the transcripts of some CaM genes were found between the rostral and caudal parts of the individual nuclei of the trigeminal system. In most cases, the CaM gene-specific transcripts displayed a clear differential distribution along the rostrocaudal axis: they were more abundant in the rostral parts of these nuclei. For example, the levels of mRNAs transcribed from each of the CaM I, II and III genes were significantly higher in the rostral part of the principal sensory trigeminal nucleus, while the rostral part of the motor trigeminal nucleus exhibited an elevated amount of transcripts for the CaM I gene only. Interestingly, the CaM II mRNAs were most abundant in the caudal part of the mesencephalic trigeminal nucleus. Moreover, the largest difference between any of the CaM gene-specific transcript contents of the rostral and caudal parts was found for those of the CaM II gene in the principal sensory trigeminal nucleus. Here, the intranuclear difference was about 50%, the rostral part being the richer in CaM II mRNAs. Our results draw attention to the possible causal relation between the differences in the neuronal circuitry of the rostral and caudal parts of these nuclei and their differential CaM gene expression. This somatotopy may have important functional implications

The expression of Ca2+/calmodulin-dependent protein kinase I in rat retina is regulated by light stimulation

AbstractCa2+/calmodulin-dependent protein kinase I (CaM-kinase I) in rat retina was analyzed by immunohistochemical analysis, Western blot analysis and kinase activity assay. Western blot analysis revealed two immunoreactive bands similar to those detected in the brain. Developmental studies revealed that CaM-kinase I expression increased in accordance with postnatal development. Expression of CaM-kinase I in the retinas of rats raised in the complete darkness markedly decreased. CaM-kinase I activity assay supported these findings. Synapsin I was shown to be a possible intrinsic substrate of CaM-kinase I in rat retina. These results elucidated that CaM-kinase I is expressed in the retina and may play an important role in the retinal functions and that the expression of CaM-kinase I is regulated by light stimulation