The maize Hairy Sheath Frayed1 (Hsf1) mutant alters leaf patterning through increased cytokinin signaling

ABSTRACTLeaf morphogenesis requires growth polarized along three axes - proximal-distal, medial-lateral and abaxial-adaxial. Grass leaves display a prominent proximal-distal (P-D) polarity consisting of a proximal sheath separated from the distal blade by the auricle and ligule. Although proper specification of the four segments is essential for normal morphology, our knowledge is incomplete regarding the mechanisms which influence P-D specification in monocots like maize (Zea mays). Here we report the identification of the gene underlying the semi-dominant, leaf patterning, maize mutant Hairy Sheath Frayed1 (Hsf1). Hsf1 plants produce leaves with outgrowths consisting of proximal segments – sheath, auricle and ligule – emanating from the distal blade margin. Analysis of three independent Hsf1 alleles revealed gain-of-function missense mutations in the ligand binding domain of the maize cytokinin (CK) receptor Zea mays Histidine Kinase1 (ZmHK1) gene. Biochemical analysis and structural modeling suggest the mutated residues near the CK binding pocket affect CK binding affinity. Treatment of wild type seedlings with exogenous CK phenocopied the Hsf1 leaf phenotypes. Results from expression and epistatic analyses indicated the Hsf1 mutant receptor appears to be hypersignaling. Our results demonstrate that hypersignaling of CK in incipient leaf primordia can reprogram developmental patterns in maize.SummaryIncreased cytokinin signaling in the maize Hairy Sheath Frayed1 mutant modifies leaf development leading to changes in pattering, growth and cell identity.

Download Full-text

Tissue distribution and developmental patterns of NADH-dependent and ferredoxin-dependent glutamate synthase activities in maize (Zea mays) kernels

Physiologia Plantarum ◽

10.1034/j.1399-3054.1991.810406.x ◽

1991 ◽

Vol 81 (4) ◽

pp. 481-488 ◽

Cited By ~ 1

Author(s):

Michael J. Muhitch

Keyword(s):

Zea Mays ◽

Tissue Distribution ◽

Glutamate Synthase ◽

Developmental Patterns

Download Full-text

The Maize Hairy Sheath Frayed1 (Hsf1) Mutation Alters Leaf Patterning through Increased Cytokinin Signaling

The Plant Cell ◽

10.1105/tpc.19.00677 ◽

2020 ◽

Vol 32 (5) ◽

pp. 1501-1518 ◽

Cited By ~ 1

Author(s):

Michael G. Muszynski ◽

Lindsay Moss-Taylor ◽

Sivanandan Chudalayandi ◽

James Cahill ◽

Angel R. Del Valle-Echevarria ◽

...

Keyword(s):

Cytokinin Signaling ◽

Leaf Patterning

Download Full-text

Tissue distribution and developmental patterns of NADH-dependent and ferredoxin-dependent glutamate synthase activities in maize (Zea mays) kernels

Physiologia Plantarum ◽

10.1111/j.1399-3054.1991.tb05088.x ◽

1991 ◽

Vol 81 (4) ◽

pp. 481-488 ◽

Cited By ~ 7

Author(s):

Michael J. Muhitch

Keyword(s):

Zea Mays ◽

Tissue Distribution ◽

Glutamate Synthase ◽

Developmental Patterns

Download Full-text

Reprogramming protein kinase substrate specificity through synthetic mutations

10.1101/091892 ◽

2016 ◽

Author(s):

Joshua M. Lubner ◽

George M. Church ◽

Michael F. Chou ◽

Daniel Schwartz

Keyword(s):

Protein Kinase ◽

Substrate Specificity ◽

Structure Function ◽

Binding Pocket ◽

Missense Mutations ◽

New Paradigm ◽

Substrate Binding Pocket ◽

Kinase Substrate ◽

Substrate Preferences ◽

Kinase Specificity

Protein kinase specificity is largely imparted through substrate binding pocket motifs. Missense mutations in these regions are frequently associated with human disease, and in some cases can alter substrate specificity. However, current efforts at decoding the influence of mutations on substrate specificity have been focused on disease-associated mutations. Here, we adapted the Proteomic Peptide Library (ProPeL) approach for determining kinase specificity to the task of exploring structure-function relationships in kinase specificity by interrogating the effects of synthetic mutation. We established a specificity model for the wild-type DYRK1A kinase with unprecedented resolution. Using existing crystallographic and sequence homology data, we rationally designed mutations that precisely reprogrammed the DYRK1A kinase at the P+1 position to mimic the substrate preferences of a related kinase, CK II. This study illustrates a new synthetic biological approach to reprogram kinase specificity by design, and a powerful new paradigm to investigate structure-function relationships underpinning kinase substrate specificity.

Download Full-text

Uptake and biochemical analysis of 2,4-D in cultured zygotic embryos of zea mays L.

Journal of Plant Physiology ◽

10.1016/s0176-1617(96)80135-0 ◽

1996 ◽

Vol 149 (3-4) ◽

pp. 363-371 ◽

Cited By ~ 5

Author(s):

F.B.F. Bronsema ◽

P. Redig ◽

W.J.F. van Oostveen ◽

H.A. van Onckelen ◽

A.A.M. van Lammeren

Keyword(s):

Zea Mays ◽

Biochemical Analysis ◽

Zea Mays L ◽

Zygotic Embryos

Download Full-text

Biochemical Analysis of Four Missense Mutations in the HSD17B3 Gene Associated With 46,XY Disorders of Sex Development in Egyptian Patients

Journal of Sexual Medicine ◽

10.1016/j.jsxm.2017.07.006 ◽

2017 ◽

Vol 14 (9) ◽

pp. 1165-1174 ◽

Cited By ~ 5

Author(s):

Roger T. Engeli ◽

Maria Tsachaki ◽

Heba A. Hassan ◽

Christoph P. Sager ◽

Mona L. Essawi ◽

...

Keyword(s):

Biochemical Analysis ◽

Disorders Of Sex Development ◽

Missense Mutations ◽

Sex Development ◽

Egyptian Patients

Download Full-text

Binding Pocket Alterations in Dihydrofolate Synthase Confer Resistance topara-Aminosalicylic Acid in Clinical Isolates of Mycobacterium tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01775-13 ◽

2013 ◽

Vol 58 (3) ◽

pp. 1479-1487 ◽

Cited By ~ 47

Author(s):

Fei Zhao ◽

Xu-De Wang ◽

Luke N. Erber ◽

Ming Luo ◽

Ai-zhen Guo ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Resistance Mechanism ◽

Binding Pocket ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Missense Mutations ◽

Aminosalicylic Acid ◽

Content Type ◽

Resistant Tuberculosis ◽

Mechanistic Basis

ABSTRACTThe mechanistic basis for the resistance ofMycobacterium tuberculosistopara-aminosalicylic acid (PAS), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. As a substrate analog of the folate precursorpara-aminobenzoic acid, PAS is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. As a result, the mutation of dihydrofolate synthase, an enzyme needed for the bioactivation of PAS, causes PAS resistance inM. tuberculosisstrain H37Rv. Here, we demonstrate that various missense mutations within the coding sequence of the dihydropteroate (H2Pte) binding pocket of dihydrofolate synthase (FolC) confer PAS resistance in laboratory isolates ofM. tuberculosisandMycobacterium bovis. From a panel of 85 multidrug-resistantM. tuberculosisclinical isolates, 5 were found to harbor mutations in thefolCgene within the H2Pte binding pocket, resulting in PAS resistance. While these alterations in the H2Pte binding pocket resulted in reduced dihydrofolate synthase activity, they also abolished the bioactivation of hydroxy dihydropteroate to hydroxy dihydrofolate. Consistent with this model for abolished bioactivation, the introduction of a wild-type copy offolCfully restored PAS susceptibility infolCmutant strains. Confirmation of this novel PAS resistance mechanism will be beneficial for the development of molecular method-based diagnostics forM. tuberculosisclinical isolates and for further defining the mode of action of this important tuberculosis drug.

Download Full-text

Biochemical analysis of mutations in P450 oxidoreductase

Biochemical Society Transactions ◽

10.1042/bst0341186 ◽

2006 ◽

Vol 34 (6) ◽

pp. 1186-1191 ◽

Cited By ~ 10

Author(s):

A.V. Pandey

Keyword(s):

Drug Metabolism ◽

Biochemical Analysis ◽

Three Dimensional ◽

Polymorphic Form ◽

Extensive Study ◽

Expression Vectors ◽

Missense Mutations ◽

Three Dimensional Model ◽

Biochemical Basis ◽

Initial Report

All microsomal P450s require POR (cytochrome P450 reductase) for catalytic activity. Most of the clinically used drugs are metabolized by a small number of P450s and polymorphisms in the cytochrome P450s are known to cause changes in drug metabolism. We have recently found a number of POR missense mutations in the patients with disordered steroidogenesis. Our initial report described five missense mutations (A284P, R454H, V489E, C566Y and V605F) identified in four patients. We built bacterial expression vectors for each POR variant, purified the membranes expressing normal or variant POR and characterized their activities with cytochrome c and P450c17 assays. We have recently completed an extensive study of the range of POR mutations and characterized the mutants/polymorphisms A112V, T139A, M260V, Y456H, A500V, G536R, L562P, R613X, V628I and F643del from sequencing of patient DNA. We also studied POR variants Y179D, P225L, R313W, G410S and G501R that were available in databases or the published literature. We analysed the mutations with a three-dimensional model of human POR that was based on an essentially similar rat POR with known crystal structure. The missense mutations found in patients with disordered steroidogenesis mapped to functionally important domains of POR and the apparent polymorphisms mapped to less crucial regions. Since a variation in POR can alter the activity of all microsomal P450s, it can also affect the drug metabolism even with a normal P450. Understanding the genetic and biochemical basis of POR-mediated drug metabolism will provide valuable information about possible differences in P450-mediated reactions among the individuals carrying a variant or polymorphic form of POR.

Download Full-text