scholarly journals P5A-ATPases control the ER translocation of Wnt for neuronal migration

2021 ◽  
Author(s):  
Tingting Li ◽  
Xiaoyan Yang ◽  
Zhigang Feng ◽  
Wang Nie ◽  
Yan Zou
Keyword(s):  
Neuronal Migration ◽  
Neuronal Development ◽  
Signal Sequence ◽  
Core Region ◽  
Hydrophobic Core ◽  
C Elegans ◽  
Wnt Proteins ◽  
Developmental Patterning ◽  
Er Targeting ◽  
Biochemical Analyses

Wnt family are conserved secreted proteins required for developmental patterning and tissue homeostasis. Research into the mechanisms that influence intracellular maturation and intercelluar signal transduction of Wnt proteins has proved fruitful. However, the knowledge of how Wnt enters into the endoplasmic reticulum (ER) for processing and secretion is still limited. Here we report that CATP-8/P5A-ATPase directs neuronal migration in C. elegans by controlling EGL-20/Wnt biogenesis. Our genetic and biochemical analyses demonstrate that CATP-8 control the ER targeting of EGL-20/Wnt through the hydrophobic core region in EGL-20 signal sequence. We further show that regulation of Wnt biogenesis by P5A-ATPase is conserved in human cells. These findings reveal physiological roles of P5A-ATPase in neuronal development and identify Wnt proteins as direct substrates of P5A-ATPase to be translocated into the ER.

scholarly journals Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4

2010 ◽  
Vol 21 (8) ◽  
pp. 1324-1334 ◽  
Author(s):  
Tomoyasu Shinoda ◽  
Hidenori Ito ◽  
Kaori Sudo ◽  
Ikuko Iwamoto ◽  
Rika Morishita ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Cell Cycle Control ◽  
Coiled Coil ◽  
Cortical Plate ◽  
Process Formation ◽  
Biochemical Analyses

Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.

Structure, function, and expression of SEL-1, a negative regulator of LIN-12 and GLP-1 in C. elegans

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 637-644 ◽  
Author(s):  
B. Grant ◽  
I. Greenwald
Keyword(s):  
Staining Pattern ◽  
Signal Sequence ◽  
Negative Regulator ◽  
Yeast Gene ◽  
Hydrophobic Region ◽  
C Elegans ◽  
Cell Ablation ◽  
New Information ◽  
Membrane Bound ◽  
Punctate Staining

Previous work indicated that sel-1 functions as a negative regulator of lin-12 activity, and predicted that SEL-1 is a secreted or membrane associated protein. In this study, we describe cell ablation experiments that suggest sel-1 mutations elevate lin-12 activity cell autonomously. We also use transgenic approaches to demonstrate that the predicted signal sequence of SEL-1 can direct secretion and is important for function, while a C-terminal hydrophobic region is not required for SEL-1 function. In addition, by analyzing SEL-1 localization using specific antisera we find that SEL-1 is localized intracellularly, with a punctate staining pattern suggestive of membrane bound vesicles. We incorporate these observations, and new information about a related yeast gene, into a proposal for a possible mechanism for SEL-1 function in LIN-12 turnover.

scholarly journals Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lingfeng Meng ◽  
Albert Zhang ◽  
Yishi Jin ◽  
Dong Yan
Keyword(s):  
Gap Junctions ◽  
Glial Cells ◽  
Neuronal Development ◽  
Dependent Manner ◽  
Critical Step ◽  
C Elegans ◽  
Calcium Dependent ◽  
Intracellular Pathways ◽  
Axon Specification

Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions.

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

scholarly journals C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development

Development ◽  
2009 ◽  
Vol 136 (7) ◽  
pp. 1201-1210 ◽  
Author(s):  
P. J. Vanderzalm ◽  
A. Pandey ◽  
M. E. Hurwitz ◽  
L. Bloom ◽  
H. R. Horvitz ◽  
...  
Keyword(s):  
Neuronal Development ◽  
C Elegans

scholarly journals Insights into the Involvement of Spliceosomal Mutations in Myelodysplastic Disorders from Analysis of SACY-1/DDX41 in Caenorhabditis elegans

Genetics ◽  
2020 ◽  
Vol 214 (4) ◽  
pp. 869-893 ◽  
Author(s):  
Tatsuya Tsukamoto ◽  
Micah D. Gearhart ◽  
Seongseop Kim ◽  
Gemechu Mekonnen ◽  
Caroline A. Spike ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Myelodysplastic Syndromes ◽  
Missense Mutations ◽  
Synthetic Lethal ◽  
C Elegans ◽  
Link Type ◽  
Dead Box ◽  
Synthetic Lethal Interactions ◽  
Biochemical Analyses ◽  
Cellular Phenotypes

Mutations affecting spliceosomal proteins are frequently found in hematological malignancies, including myelodysplastic syndromes and acute myeloid leukemia (AML). DDX41/Abstrakt is a metazoan-specific spliceosomal DEAD-box RNA helicase that is recurrently mutated in inherited myelodysplastic syndromes and in relapsing cases of AML. The genetic properties and genomic impacts of disease-causing missense mutations in DDX41 and other spliceosomal proteins have been uncertain. Here, we conduct a comprehensive analysis of the Caenorhabditis elegans DDX41 ortholog, SACY-1. Biochemical analyses defined SACY-1 as a component of the C. elegans spliceosome, and genetic analyses revealed synthetic lethal interactions with spliceosomal components. We used the auxin-inducible degradation system to analyze the consequence of SACY-1 depletion on the transcriptome using RNA sequencing. SACY-1 depletion impacts the transcriptome through splicing-dependent and splicing-independent mechanisms. Altered 3′ splice site usage represents the predominant splicing defect observed upon SACY-1 depletion, consistent with a role for SACY-1 in the second step of splicing. Missplicing events appear more prevalent in the soma than the germline, suggesting that surveillance mechanisms protect the germline from aberrant splicing. The transcriptome changes observed after SACY-1 depletion suggest that disruption of the spliceosome induces a stress response, which could contribute to the cellular phenotypes conferred by sacy-1 mutant alleles. Multiple sacy-1/ddx41 missense mutations, including the R525H human oncogenic variant, confer antimorphic activity, suggesting that their incorporation into the spliceosome is detrimental. Antagonistic variants that perturb the function of the spliceosome may be relevant to the disease-causing mutations, including DDX41, affecting highly conserved components of the spliceosome in humans.

scholarly journals Laterally Orienting C. elegans Using Geometry at Microscale for High-Throughput Visual Screens in Neurodegeneration and Neuronal Development Studies

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35037 ◽  
Author(s):  
Ivan de Carlos Cáceres ◽  
Nicholas Valmas ◽  
Massimo A. Hilliard ◽  
Hang Lu
Keyword(s):  
High Throughput ◽  
Neuronal Development ◽  
Development Studies ◽  
C Elegans

scholarly journals Growth Arrest-Specific Gene 6 (Gas6)/Adhesion Related Kinase (Ark) Signaling Promotes Gonadotropin-Releasing Hormone Neuronal Survival via Extracellular Signal-Regulated Kinase (ERK) and Akt

1999 ◽  
Vol 13 (2) ◽  
pp. 191-201 ◽  
Author(s):  
Melissa P. Allen ◽  
Chan Zeng ◽  
Kristina Schneider ◽  
Xiaoyan Xiong ◽  
Mary Kay Meintzer ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neuronal Migration ◽  
Neuronal Development ◽  
Mek Inhibitor ◽  
Specific Gene ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Gnrh Neurons ◽  
Induced Apoptosis

Abstract We identified Ark, the mouse homolog of the receptor tyrosine kinase Axl (Ufo, Tyro7), in a screen for novel factors involved in GnRH neuronal migration by using differential-display PCR on cell lines derived at two windows during GnRH neuronal development. Ark is expressed in Gn10 GnRH cells, developed from a tumor in the olfactory area when GnRH neurons are migrating, but not in GT1–7 cells, derived from a tumor in the forebrain when GnRH neurons are postmigratory. Since Ark (Axl) signaling protects from programmed cell death in fibroblasts, we hypothesized that it may play an antiapoptotic role in GnRH neurons. Gn10 (Ark positive) GnRH cells were more resistant to serum withdrawal-induced apoptosis than GT1–7 (Ark negative) cells, and this effect was augmented with the addition of Gas6, the Ark (Axl) ligand. Gas6/Ark stimulated the extracellular signal-regulated kinase, ERK, and the serine-threonine kinase, Akt, a downstream component of the phosphoinositide 3-kinase (PI3-K) pathway. To determine whether ERK or Akt activation is required for the antiapoptotic effects of Gas6/Ark in GnRH neurons, cells were serum starved in the absence or presence of Gas6, with or without inhibitors of ERK and PI3-K signaling cascades. Gas6 rescued Gn10 cells from apoptosis, and this effect was blocked by coincubation of the cells with the mitogen-activated protein/ERK kinase (MEK) inhibitor, PD98059, or wortmannin (but not rapamycin). These data support an important role for Gas6/Ark signaling via the ERK and PI3-K (via Akt) pathways in the protection of GnRH neurons from programmed cell death across neuronal migration.

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