scholarly journals CRMP4-mediated fornix development involves semaphorin-3E signaling pathway

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Benoît Boulan ◽  
Charlotte Ravanello ◽  
Amandine Peyrel ◽  
Christophe Bosc ◽  
Christian Delphin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cognitive Abilities ◽  
Axonal Guidance ◽  
Psychiatric Diseases ◽  
Receptor Complex ◽  
Axonal Pathfinding ◽  
Collapsin Response Mediator Protein ◽  
Guidance Cue ◽  
Mediator Protein ◽  
Growth Promoting

Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-Associated Protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the Collapsin Response Mediator Protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within Detergent-Resistant Membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E's growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

scholarly journals Neurite Outgrowth and Morphological Changes Induced by 8-trans Unsaturation of Sphingadienine in kCer Molecular Species

2019 ◽  
Vol 20 (9) ◽  
pp. 2116 ◽  
Author(s):  
Seigo Usuki ◽  
Noriko Tamura ◽  
Tomohiro Tamura ◽  
Kunikazu Tanji ◽  
Daisuke Mikami ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Neurite Outgrowth ◽  
Signaling Pathway ◽  
Molecular Species ◽  
Morphological Changes ◽  
Semaphorin 3A ◽  
Collapsin Response Mediator Protein ◽  
Trans Unsaturation ◽  
Pathway Activation ◽  
Mediator Protein

Konjac ceramide (kCer), which consists of plant-type molecular species of characteristic shingoid bases and fatty acids, is prepared from konjac glucosylceramide GlcCer by chemoenzymatical deglucosylation. kCer activates the semaphorin 3A (Sema3A) signaling pathway, inducing collapsin response mediator protein 2 (CRMP2) phosphorylation. This results in neurite outgrowth inhibition and morphological changes in remaining long neurites in PC12 cells. Whether a specific molecular species of kCer can bind to the Sema3A receptor (Neuropilin1, Nrp1) and activate the Sema3A signaling pathway remains unknown. Here, we prepared kCer molecular species using endoglycoceramidase I-mediated deglucosylation and examined neurite outgrowth and phosphorylation of collapsin response mediator protein 2 in nerve growth factor (NGF)-primed cells. The 8-trans unsaturation of sphingadienine of kCer was essential for Sema3A-like signaling pathway activation. Conversely, 8-cis unsaturation of kCer molecular species had no effect on Sema3A-like activation, and neurite outgrowth inhibition resulted in remaining short neurites. In addition, α-hydroxylation of fatty acids was not associated with the Sema3A-like activity of the kCer molecular species. These results suggest that 8-trans or 8-cis isomerization of sphingadienine determines the specific interactions at the ligand-binding site of Nrp1.

scholarly journals Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules

Zygote ◽  
2021 ◽  
pp. 1-12
Author(s):  
Zhen Jin ◽  
Hua-Feng Shou ◽  
Jin-Wei Liu ◽  
Shan-Shan Jiang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Spindle Microtubule ◽  
Collapsin Response Mediator Protein ◽  
Microtubule Severing ◽  
Structural Support ◽  
Mediator Protein ◽  
Spindle Microtubules ◽  
Transportation Routes ◽  
Normal Meiosis

Abstract Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

scholarly journals Glycosylation in Axonal Guidance

2021 ◽  
Vol 22 (10) ◽  
pp. 5143
Author(s):  
Sampada P. Mutalik ◽  
Stephanie L. Gupton
Keyword(s):  
Neuronal Development ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Axonal Pathfinding ◽  
Guidance Cues ◽  
Functional Implications ◽  
Protein Functions ◽  
Guidance Receptors ◽  
Surface Localization

How millions of axons navigate accurately toward synaptic targets during development is a long-standing question. Over decades, multiple studies have enriched our understanding of axonal pathfinding with discoveries of guidance molecules and morphogens, their receptors, and downstream signalling mechanisms. Interestingly, classification of attractive and repulsive cues can be fluid, as single guidance cues can act as both. Similarly, guidance cues can be secreted, chemotactic cues or anchored, adhesive cues. How a limited set of guidance cues generate the diversity of axonal guidance responses is not completely understood. Differential expression and surface localization of receptors, as well as crosstalk and spatiotemporal patterning of guidance cues, are extensively studied mechanisms that diversify axon guidance pathways. Posttranslational modification is a common, yet understudied mechanism of diversifying protein functions. Many proteins in axonal guidance pathways are glycoproteins and how glycosylation modulates their function to regulate axonal motility and guidance is an emerging field. In this review, we discuss major classes of glycosylation and their functions in axonal pathfinding. The glycosylation of guidance cues and guidance receptors and their functional implications in axonal outgrowth and pathfinding are discussed. New insights into current challenges and future perspectives of glycosylation pathways in neuronal development are discussed.

scholarly journals Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Garima Sharma ◽  
Ashish Ranjan Sharma ◽  
Eun-Min Seo ◽  
Ju-Suk Nam
Keyword(s):  
Genetic Polymorphism ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
The Other ◽  
Present Review ◽  
Receptor Complex ◽  
Related Proteins ◽  
Related Association

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue

2015 ◽  
Vol 9 (9-10) ◽  
pp. 817-831 ◽  
Author(s):  
Daniel Martins-de-Souza ◽  
Juliana S. Cassoli ◽  
Juliana M. Nascimento ◽  
Kenneth Hensley ◽  
Paul C. Guest ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Collapsin Response Mediator Protein ◽  
Protein Interactome ◽  
Mediator Protein ◽  
Partner Proteins

scholarly journals Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells

2018 ◽  
Vol 314 (4) ◽  
pp. F630-F642 ◽  
Author(s):  
Kamala Sundararaj ◽  
Jessalyn I. Rodgers ◽  
Subathra Marimuthu ◽  
Leah J. Siskind ◽  
Evelyn Bruner ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Signaling Pathway ◽  
Mesangial Cells ◽  
Morbidity And Mortality ◽  
Receptor Complex ◽  
Catabolic Pathway ◽  
Neuraminidase Activity ◽  
Complex Signaling

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

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