Thioredoxin-family protein EYE2 and Ser/Thr kinase EYE3 play interdependent roles in eyespot assembly

The eyespot of the biflagellate unicellular green alga Chlamydomonas reinhardtii is a complex organelle that facilitates directional responses of the cell to environmental light stimuli. The eyespot, which assembles de novo after every cell division and is associated with the daughter four-membered (D4) microtubule rootlet, comprises an elliptical patch of rhodopsin photoreceptors on the plasma membrane and stacks of carotenoid-rich pigment granule arrays in the chloroplast. Two loci, EYE2 and EYE3, define factors involved in the formation and organization of the eyespot pigment granule arrays. Whereas EYE3, a serine/threonine kinase of the ABC1 family, localizes to pigment granules, EYE2 localization corresponds to an area of the chloroplast envelope in the eyespot. EYE2 is positioned along, and adjacent to, the D4 rootlet in the absence of pigment granules. The eyespot pigment granule array is required for maintenance of the elliptical shape of both the overlying EYE2 and channelrhodopsin-1 photoreceptor patches. We propose a model of eyespot assembly wherein rootlet and photoreceptor direct EYE2 to an area of the chloroplast envelope, where it acts to facilitate assembly of pigment granule arrays, and EYE3 plays a role in the biogenesis of the pigment granules.

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Pigment granule migration in crustacean photoreceptors requires calcium

Visual Neuroscience ◽

10.1017/s0952523800007112 ◽

1996 ◽

Vol 13 (1) ◽

pp. 43-49 ◽

Cited By ~ 3

Author(s):

Christina King-Smith ◽

Thomas W. Cronin

Keyword(s):

Pigment Granule ◽

Size And Shape ◽

Pigment Granules ◽

Gradual Loss ◽

Light Stimuli ◽

Pigment Granule Migration ◽

Normal Calcium

AbstractWe have investigated the role of calcium in the regulation of pigment granule migration in photoreceptors of the semi-terrestrial crab, Sesarma cinereum. Isolated crab eyes (eyecup plus eyestalk) were maintained in crustacean Ringer either prepared normally or calcium-free plus 50 mM EGTA. Pigment granule movement was indirectly observed by monitoring reflectance from the eye during light stimuli using intracellular optical physiological techniques. Electroretinograms (ERGs) were also measured during light stimuli. EGTA treatment caused gradual loss of centripetal migration of pigment granules (normally leading to pupillary closure), and photoreceptors eventually became locked in the open-pupil, dark-adapted state despite repeated stimuli. In contrast, ERG responses continued throughout EGTA treatment, although the size and shape ofthe response was altered. Normal ERG responses and pigment granule movements returned after replacing EGTA-Ringer with normal-calcium medium. These results suggest that centripetal migration of pigment granules in crustacean photoreceptors requires calcium.

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The Clinical Picture of a Bilateral Perisylvian Syndrome as the Initial Symptom of Mega-Corpus-Callosum Syndrome due to a MAST1-Gene Mutation

Neuropediatrics ◽

10.1055/s-0040-1710588 ◽

2020 ◽

Vol 51 (06) ◽

pp. 435-439

Author(s):

Laura Hecher ◽

Jessika Johannsen ◽

Tatjana Bierhals ◽

Jan-Hendrik Buhk ◽

Maja Hempel ◽

...

Keyword(s):

Corpus Callosum ◽

Clinical Picture ◽

De Novo ◽

De Novo Mutation ◽

Global Developmental Delay ◽

Initial Symptom ◽

Imaging Features ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Migration Disorder

AbstractCongenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder associated with typical clinical and imaging features such as bilateral symmetrical polymicrogyria, either exclusively or mainly affecting the perisylvian region of the brain. We present a girl with the typical clinical picture of a CBPS and a complex migration disorder, predominantly presenting as bilateral symmetrical polymicrogyria associated with corpus callosum hyperplasia, ventricular dilation, and pontine hypoplasia. At the age of 6 months, the girl showed a profound global developmental delay, seizures refractory to treatment, and severe oromotor dysfunction. Exome analysis revealed a de novo mutation in microtubule-associated serine/threonine kinase 1 (MAST1). Recently, mutations in this gene were described in six patients with a cortical migration disorder named mega-corpus-callosum syndrome with cerebellar hypoplasia. Although all patients present the clinical and imaging features of CBPS, a clear assignment between CBPS and MAST1 mutations has not been reported yet.

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IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

Blood ◽

10.1182/blood-2008-04-149419 ◽

2008 ◽

Vol 112 (10) ◽

pp. 3949-3958 ◽

Cited By ~ 72

Author(s):

Svetlana A. Didichenko ◽

Nicole Spiegl ◽

Thomas Brunner ◽

Clemens A. Dahinden

Keyword(s):

Immune Responses ◽

De Novo ◽

Pi3 Kinase ◽

Protein Transduction ◽

Wild Type ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Antiapoptotic Proteins ◽

Tat Fusion Proteins ◽

Human Basophils

Abstract The contribution of basophils in allergic disease and other Th2-type immune responses depends on their persistence at sites of inflammation, but the ligands and molecular pathways supporting basophil survival are largely unknown. The comparison of rates of apoptosis and of the expression of antiapoptotic proteins in different human granulocyte types revealed that basophils have a considerably longer spontaneous life span than neutrophils and eosinophils consistent with high levels of constitutive Bcl-2 expression. Interleukin-3 (IL-3) is the only ligand that efficiently protects basophils from apoptosis as evidenced by screening a large number of stimuli. IL-3 up-regulates the expression of the antiapoptotic proteins cIAP2, Mcl-1, and Bcl-XL and induces a rapid and sustained de novo expression of the serine/threonine kinase Pim1 that closely correlates with cytokine-enhanced survival. Inhibitor studies and protein transduction of primary basophils using wild-type and kinase-dead Pim1-Tat fusion-proteins demonstrate the functional importance of Pim1 induction in the IL-3–enhanced survival. Our data further indicate that the antiapoptotic Pim1-mediated pathway operates independently of PI3-kinase but involves the activation of p38 MAPK. The induction of Pim1 leading to PI3-kinase–independent survival as described here for basophils may also be a relevant antiapoptotic mechanism in other terminally differentiated leukocyte types.

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De novo germline mutation in the serine-threonine kinase STK11/LKB1 gene associated with Peutz-Jeghers syndrome

Clinical Genetics ◽

10.1111/j.0009-9163.2004.00266.x ◽

2004 ◽

Vol 66 (1) ◽

pp. 58-62 ◽

Cited By ~ 21

Author(s):

I Hernan ◽

I Roig ◽

B Martin ◽

M J Gamundi ◽

M Martinez-Gimeno ◽

...

Keyword(s):

Germline Mutation ◽

De Novo ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Peutz Jeghers Syndrome

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The Role of Microtubule Associated Serine/Threonine Kinase 3 Variants in Neurodevelopmental Diseases: Genotype-Phenotype Association

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.775479 ◽

2022 ◽

Vol 14 ◽

Author(s):

Li Shu ◽

Neng Xiao ◽

Jiong Qin ◽

Qi Tian ◽

Yanghui Zhang ◽

...

Keyword(s):

Exome Sequencing ◽

Large Scale ◽

De Novo ◽

Sequencing Data ◽

Phenotype Correlation ◽

Serine Threonine Kinase ◽

Zebrafish Model ◽

Threonine Kinase ◽

Missense Variants ◽

Genotype Phenotype Correlation

Objective: To prove microtubule associated serine/threonine kinase 3 (MAST3) gene is associated with neurodevelopmental diseases (NDD) and the genotype-phenotype correlation.Methods: Trio exome sequencing (trio ES) was performed on four NDD trios. Bioinformatic analysis was conducted based on large-scale genome sequencing data and human brain transcriptomic data. Further in vivo zebrafish studies were performed.Results: In our study, we identified four de novo MAST3 variants (NM_015016.1: c.302C > T:p.Ser101Phe; c.311C > T:p.Ser104Leu; c.1543G > A:p.Gly515Ser; and c.1547T > C:p.Leu516Pro) in four patients with developmental and epileptic encephalopathy (DEE) separately. Clinical heterogeneities were observed in patients carrying variants in domain of unknown function (DUF) and serine-threonine kinase (STK) domain separately. Using the published large-scale exome sequencing data, higher CADD scores of missense variants in DUF domain were found in NDD cohort compared with gnomAD database. In addition, we obtained an excess of missense variants in DUF domain when compared autistic spectrum disorder (ASD) cohort with gnomAD database, similarly an excess of missense variants in STK domain when compared DEE cohort with gnomAD database. Based on Brainspan datasets, we showed that MAST3 expression was significantly upregulated in ASD and DEE-related brain regions and was functionally linked with DEE genes. In zebrafish model, abnormal morphology of central nervous system was observed in mast3a/b crispants.Conclusion: Our results support the possibility that MAST3 is a novel gene associated with NDD which could expand the genetic spectrum for NDD. The genotype-phenotype correlation may contribute to future genetic counseling.

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C2 Domain Protein MIN1 Promotes Eyespot Organization in Chlamydomonas reinhardtii

Eukaryotic Cell ◽

10.1128/ec.00118-08 ◽

2008 ◽

Vol 7 (12) ◽

pp. 2100-2112 ◽

Cited By ~ 12

Author(s):

Telsa M. Mittelmeier ◽

Peter Berthold ◽

Avihai Danon ◽

Mary Rose Lamb ◽

Alexander Levitan ◽

...

Keyword(s):

Plasma Membrane ◽

Chlamydomonas Reinhardtii ◽

Domain Architecture ◽

Pigment Granule ◽

Chloroplast Envelope ◽

C2 Domain ◽

Photoautotrophic Growth ◽

Unicellular Green Alga ◽

Mutant Cells ◽

Phenotypic Rescue

ABSTRACT Assembly and asymmetric localization of the photosensory eyespot in the biflagellate, unicellular green alga Chlamydomonas reinhardtii requires coordinated organization of photoreceptors in the plasma membrane and pigment granule/thylakoid membrane layers in the chloroplast. min1 (mini-eyed) mutant cells contain abnormally small, disorganized eyespots in which the chloroplast envelope and plasma membrane are no longer apposed. The MIN1 gene, identified here by phenotypic rescue, encodes a protein with an N-terminal C2 domain and a C-terminal LysM domain separated by a transmembrane sequence. This novel domain architecture led to the hypothesis that MIN1 is in the plasma membrane or the chloroplast envelope, where membrane association of the C2 domain promotes proper eyespot organization. Mutation of conserved C2 domain loop residues disrupted association of the MIN1 C2 domain with the chloroplast envelope in moss cells but did not abolish eyespot assembly in Chlamydomonas. In min1 null cells, channelrhodopsin-1 (ChR1) photoreceptor levels were reduced, indicating a role for MIN1 in ChR1 expression and/or stability. However, ChR1 localization was only minimally disturbed during photoautotrophic growth of min1 cells, conditions under which the pigment granule layers are disorganized. The data are consistent with the hypothesis that neither MIN1 nor proper organization of the plastidic components of the eyespot is essential for localization of ChR1.

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