scholarly journals Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev192674
Author(s):  
Cansu Akkaya ◽  
Dila Atak ◽  
Altug Kamacioglu ◽  
Busra Aytul Akarlar ◽  
Gokhan Guner ◽  
...  
Keyword(s):  
Brain Development ◽  
Cortical Neurons ◽  
Splice Variants ◽  
Developmentally Regulated ◽  
Spindle Poles ◽  
Brain Malformations ◽  
In The Wild ◽  
Interactome Mapping ◽  
Alternative Splice Variants ◽  
Alternative Isoforms

ABSTRACTKIF2A is a kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. However, how different KIF2A alternative isoforms function during development of the cerebral cortex is not known. Here, we focus on three Kif2a isoforms expressed in the developing cortex. We show that Kif2a is essential for dendritic arborization in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons; a third isoform, lacking a key N-terminal region, is ineffective. By proximity-based interactome mapping for individual isoforms, we identify previously known KIF2A interactors, proteins localized to the mitotic spindle poles and, unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to organelles, prominently to the mitochondria. In addition, we show that a KIF2A mutation, which causes brain malformations in humans, has extensive changes to its proximity-based interactome, with depletion of mitochondrial proteins identified in the wild-type KIF2A interactome. Our data raises new insights about the importance of alternative splice variants during brain development.

scholarly journals Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation

2020 ◽  
Author(s):  
Cansu Akkaya ◽  
Dila Atak ◽  
Altug Kamacioglu ◽  
Busra Aytul Akarlar ◽  
Gokhan Guner ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Protein Function ◽  
Cortical Neurons ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Developmentally Regulated ◽  
Spindle Poles ◽  
Alternatively Spliced ◽  
Interactome Mapping ◽  
Insight Into

AbstractKIF2A is a microtubule-depolymerizing kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. KIF2A is alternatively spliced in nervous tissue by specific RNA-binding proteins. However, how different KIF2A isoforms function during development of the cerebral cortex is not known. Here, we focus on three Kif2a isoforms expressed in mouse embryonic and postnatal cerebral cortex. We show that KIF2A is essential for dendritic pruning of primary cortical neurons in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons while a third isoform, lacking a key stretch of twenty amino acids, is ineffective. By proximity-labeling-based interactome mapping for individual KIF2A isoforms, we provide novel insight into how isoform specific interactions can confer changes to KIF2A protein function. Our interactome mapping identifies previously known KIF2A interactors, proteins localized to the mitotic spindle poles, and unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to the mitochondria and ER, suggesting a novel transport function for KIF2A.

scholarly journals TAPAS: tools to assist the targeted protein quantification of human alternative splice variants

2014 ◽  
Vol 30 (20) ◽  
pp. 2989-2990 ◽  
Author(s):  
Jae-Seong Yang ◽  
Eduard Sabidó ◽  
Luis Serrano ◽  
Christina Kiel
Keyword(s):  
Alternative Splice ◽  
Splice Variants ◽  
Protein Quantification ◽  
Alternative Splice Variants

scholarly journals Characterization of cortical neurons that transiently express TH during rat brain development

2006 ◽  
Vol 295 (1) ◽  
pp. 405
Author(s):  
Steve Asmus ◽  
Mark Ball ◽  
Angela Bohnen ◽  
Kevin Phelps ◽  
Cindy Hartley ◽  
...  
Keyword(s):  
Brain Development ◽  
Rat Brain ◽  
Cortical Neurons

scholarly journals Mutation analysis and characterization of alternative splice variants of the Wilson disease gene ATP7B

Hepatology ◽  
2010 ◽  
Vol 52 (5) ◽  
pp. 1662-1670 ◽  
Author(s):  
Lei Wan ◽  
Chang-Hai Tsai ◽  
Chin-Moo Hsu ◽  
Chin-Chang Huang ◽  
Chih-Chao Yang ◽  
...  
Keyword(s):  
Alternative Splice ◽  
Mutation Analysis ◽  
Wilson Disease ◽  
Disease Gene ◽  
Splice Variants ◽  
Alternative Splice Variants

Characterization of three alternative splice variants associated with the Arabidopsis rhomboid protein gene At1g74130

Botany ◽  
2013 ◽  
Vol 91 (12) ◽  
pp. 840-849 ◽  
Author(s):  
Joshua Powles ◽  
Katharine Sedivy-Haley ◽  
Eric Chapman ◽  
Kenton Ko
Keyword(s):  
Alternative Splicing ◽  
Alternative Splice ◽  
Splice Variant ◽  
Serine Proteases ◽  
Transmembrane Domain ◽  
Splice Variants ◽  
Genes Encoding ◽  
Different Characteristics ◽  
Alternative Splice Variants

Rhomboid serine proteases are grouped into three main types — secretases, presenilin-like associated rhomboid-like (PARL) proteases, and “inactive” rhomboid proteins. Although the three rhomboid groups are distinct, the different types are likely to operate within the same cell or compartment, such as observed in the plastids of Arabidopsis. There are four distinct plastid rhomboid genes at play in Arabidopsis plastids, two for active types (At1g25290 and At5g25752) and two for inactive forms (At1g74130 and At1g74140). The number of working plastid rhomboids is further increased by alternative splicing, as reported for At1g25290. To understand how the plastid rhomboid system works, it is necessary to identify all rhomboid forms in play. To this end, this study was designed to examine the alternative splicing activities of At1g74130, one of the two genes encoding proteolytically “inactive” plastid rhomboids. The exon mapping and DNA sequencing results obtained here indicate the presence of three prominent alternative splice variants in the At1g74130 transcript population. The dominant splice variant, L, encodes the full-length protein. The other two splice variants, M and S, produce proteins lacking sections from the carboxyl transmembrane domain region. The splice variants M and S appear to be at levels with functional potential and appear to adjust relative to each other during development and in response to changes in the level of Tic40, a component of the plastid translocon. The splice variant proteins themselves exhibit different characteristics with respect to rhomboid protein–substrate interactions. These differences were observed in bacterial co-expression pull-down assays and in yeast mitochondrial studies. When considered together, the data suggest that the alternative splicing of At1g74130 bears functional significance in Arabidopsis and is likely to be part of a mechanism for diversifying plastid rhomboid function.

scholarly journals Dab2IP Regulates Neuronal Positioning, Rap1 Activity and Integrin Signaling in the Developing Cortex

2015 ◽  
Vol 37 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Shuhong Qiao ◽  
Ramin Homayouni
Keyword(s):  
Brain Development ◽  
Cortical Neurons ◽  
Ventricular Zone ◽  
Physiological Role ◽  
Immunohistochemical Analysis ◽  
Superficial Layer ◽  
Tumor Formation ◽  
Intermediate Zone ◽  
Cortical Plate ◽  
Integrin Signaling

Dab2IP (DOC-2/DAB2 interacting protein) is a GTPase-activating protein which is involved in various aspects of brain development in addition to its roles in tumor formation and apoptosis in other systems. In this study, we carefully examined the expression profile of Dab2IP and investigated its physiological role during brain development using a Dab2IP-knockdown (KD) mouse model created by retroviral insertion of a LacZ-encoding gene-trapping cassette. LacZ staining revealed that Dab2IP is expressed in the ventricular zone as well as the cortical plate and the intermediate zone. Immunohistochemical analysis showed that Dab2IP protein is localized in the leading process and proximal cytoplasmic regions of migrating neurons in the intermediate zone. Bromodeoxyuridine birth dating experiments in combination with immunohistochemical analysis using layer-specific markers showed that Dab2IP is important for proper positioning of a subset of layer II-IV neurons in the developing cortex. Notably, neuronal migration was not completely disrupted in the cerebral cortex of Dab2IP-KD mice and disruption of migration was not strictly layer specific. Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin signaling and somal translocation in the superficial layer of the cortical plate through integrin signaling. Therefore, we examined whether Rap1 and integrin signaling were affected in Dab2IP-KD brains. We found that Dab2IP-KD resulted in higher levels of activated Rap1 and integrin in the developing cortex. Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling.

Novel alternative splice variants of NFIX and their diverse mRNA expression patterns in dairy goat

Gene ◽  
2015 ◽  
Vol 569 (2) ◽  
pp. 250-258 ◽  
Author(s):  
Xiaoyan Zhang ◽  
Yang Zhou ◽  
Chuanying Pan ◽  
Chuzhao Lei ◽  
Ruihua Dang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Alternative Splice ◽  
Splice Variants ◽  
Expression Patterns ◽  
Dairy Goat ◽  
Alternative Splice Variants

Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors

FEBS Letters ◽  
2001 ◽  
Vol 487 (3) ◽  
pp. 377-383 ◽  
Author(s):  
Laurence Mery ◽  
Fabrice Magnino ◽  
Karin Schmidt ◽  
Karl-Heinz Krause ◽  
Jean-François Dufour
Keyword(s):  
Alternative Splice ◽  
Splice Variants ◽  
Terminal Portion ◽  
Inositol 1,4,5 Trisphosphate ◽  
Alternative Splice Variants

scholarly journals Alternative Splice Variants of the Human PKR Protein Kinase Possessing Different 5′-Untranslated Regions: Expression in Untreated and Interferon-Treated Cells and Translational Activity

Virology ◽  
1999 ◽  
Vol 264 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Ken Kawakubo ◽  
Kelli L. Kuhen ◽  
Jill W. Vessey ◽  
Cyril X. George ◽  
Charles E. Samuel
Keyword(s):  
Protein Kinase ◽  
Alternative Splice ◽  
Splice Variants ◽  
Untranslated Regions ◽  
Translational Activity ◽  
Alternative Splice Variants

scholarly journals mGluR6 Transcripts in Non-neuronal Tissues

2011 ◽  
Vol 59 (12) ◽  
pp. 1076-1086 ◽  
Author(s):  
Tamar Vardi ◽  
Marie Fina ◽  
Lingli Zhang ◽  
Anuradha Dhingra ◽  
Noga Vardi
Keyword(s):  
Transgenic Mouse ◽  
Metabotropic Glutamate Receptors ◽  
Fluorescent Protein ◽  
Splice Variants ◽  
Subcommissural Organ ◽  
Wild Type Mouse ◽  
Cell Types ◽  
Protein Product ◽  
Wild Type ◽  
In The Wild

To study mGluR6 expression, the authors investigated two transgenic mouse lines that express enhanced green fluorescent protein (GFP) under control of mGluR6 promoter. In retina, GFP was expressed exclusively in all ON bipolar cell types, either uniformly across all cells of this class (line 5) or in a mosaic (patchy) fashion (line 1). In brain, GFP was found in certain cortical areas, superior colliculus, axons of the corpus callosum, accessory olfactory bulb, and cells of the subcommissural organ. Outside the nervous system, GFP was seen in the corneal endothelium, testis, the kidney’s medulla, collecting ducts and parietal layer that surround the glomeruli, and B lymphocytes. Furthermore, RT-PCR showed that most tissues that expressed GFP in the transgenic mouse also transcribed two splice variants of mGluR6 in the wild-type mouse. The alternate variant was lacking exon 8, predicting a protein product of 545 amino acids that lacks the 7-transmembrane domains of the receptor. In cornea, immunostaining for mGluR6 gave strong staining in the endothelium, and this was stronger in wild-type than in mGluR6-null mice. Furthermore, calcium imaging with Fura-2 showed that application of L-AP4, an agonist for group III metabotropic glutamate receptors including mGluR6, elevated calcium in endothelial cells.

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