Cis-combination of the classic perS and perL mutations results in arrhythmic Drosophila with ectopic accumulation of hyperphosphorylated PERIOD protein

Hyuk Wan Ko, Suzanne DiMassa, Young Kim Eun, Kiho Bae, Isaac Edery

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The 1st circadian "clock" gene identified was the X-linked period (per) gene in Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer (1971) characterized 3 alleles of per that shortened (perS; ∼19 h), lengthened (per L; ∼29 h), or abolished (per0) circadian behavioral rhythms. They also showed that transheterozygotes carrying the perS and perL mutations exhibit robust behavioral rhythms with nearly normal periods of ∼23 h, highlighting the semidominant nature of many clock mutants. In this study, per0 flies bearing a doubly mutated per transgene that carries both the per S and perL alleles (per0; per S/L) were analyzed for behavioral and molecular rhythms. Unlike singly mutated versions, the per0;perS/L transgenic flies are arrhythmic in constant dark conditions and exhibit little, if any, entrainment to daily light-dark cycles. In a wildtype per+ background, expression of perS/L abolishes behavioral rhythms, indicating that it functions in a transdominant negative fashion. Biochemical analysis of head extracts revealed that only hyperphosphorylated isoforms of the PERS/L protein are detected throughout a daily cycle, and the levels remain constant. Intriguingly, little if any PERS/L is observed in key pacemaker neurons that control daily activity rhythms, consistent with the notion that hyperphosphorylated isoforms of PER are unstable. Nonetheless, PERS/L is detected in ectopic cells in the brain, in which it exhibits an unusual localization, mainly staining the periphery of the nucleus. These results suggest that posttranslational mechanisms play a key role in limiting the accumulation of PER to specific cells. On a broader scope, our results indicate that the semidominant effects of period-altering alleles observed in trans are not necessarily preserved in the cis-configuration and that novel phenotypes can emerge.

Original languageEnglish
Pages (from-to)488-501
Number of pages14
JournalJournal of Biological Rhythms
Volume22
Issue number6
DOIs
Publication statusPublished - 2007 Dec 1

Fingerprint

Drosophila
Alleles
S Phase
Diptera
Mutation
Protein Isoforms
X-Linked Genes
Circadian Clocks
Proteins
Photoperiod
Circadian Rhythm
Drosophila melanogaster
Transgenes
Head
Staining and Labeling
Phenotype
Neurons
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

@article{2b56d57e150b441e9b5ff3b513ec7f76,
title = "Cis-combination of the classic perS and perL mutations results in arrhythmic Drosophila with ectopic accumulation of hyperphosphorylated PERIOD protein",
abstract = "The 1st circadian {"}clock{"} gene identified was the X-linked period (per) gene in Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer (1971) characterized 3 alleles of per that shortened (perS; ∼19 h), lengthened (per L; ∼29 h), or abolished (per0) circadian behavioral rhythms. They also showed that transheterozygotes carrying the perS and perL mutations exhibit robust behavioral rhythms with nearly normal periods of ∼23 h, highlighting the semidominant nature of many clock mutants. In this study, per0 flies bearing a doubly mutated per transgene that carries both the per S and perL alleles (per0; per S/L) were analyzed for behavioral and molecular rhythms. Unlike singly mutated versions, the per0;perS/L transgenic flies are arrhythmic in constant dark conditions and exhibit little, if any, entrainment to daily light-dark cycles. In a wildtype per+ background, expression of perS/L abolishes behavioral rhythms, indicating that it functions in a transdominant negative fashion. Biochemical analysis of head extracts revealed that only hyperphosphorylated isoforms of the PERS/L protein are detected throughout a daily cycle, and the levels remain constant. Intriguingly, little if any PERS/L is observed in key pacemaker neurons that control daily activity rhythms, consistent with the notion that hyperphosphorylated isoforms of PER are unstable. Nonetheless, PERS/L is detected in ectopic cells in the brain, in which it exhibits an unusual localization, mainly staining the periphery of the nucleus. These results suggest that posttranslational mechanisms play a key role in limiting the accumulation of PER to specific cells. On a broader scope, our results indicate that the semidominant effects of period-altering alleles observed in trans are not necessarily preserved in the cis-configuration and that novel phenotypes can emerge.",
author = "Ko, {Hyuk Wan} and Suzanne DiMassa and Eun, {Young Kim} and Kiho Bae and Isaac Edery",
year = "2007",
month = "12",
day = "1",
doi = "10.1177/0748730407306929",
language = "English",
volume = "22",
pages = "488--501",
journal = "Journal of Biological Rhythms",
issn = "0748-7304",
publisher = "SAGE Publications Inc.",
number = "6",

}

Cis-combination of the classic perS and perL mutations results in arrhythmic Drosophila with ectopic accumulation of hyperphosphorylated PERIOD protein. / Ko, Hyuk Wan; DiMassa, Suzanne; Eun, Young Kim; Bae, Kiho; Edery, Isaac.

In: Journal of Biological Rhythms, Vol. 22, No. 6, 01.12.2007, p. 488-501.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cis-combination of the classic perS and perL mutations results in arrhythmic Drosophila with ectopic accumulation of hyperphosphorylated PERIOD protein

AU - Ko, Hyuk Wan

AU - DiMassa, Suzanne

AU - Eun, Young Kim

AU - Bae, Kiho

AU - Edery, Isaac

PY - 2007/12/1

Y1 - 2007/12/1

N2 - The 1st circadian "clock" gene identified was the X-linked period (per) gene in Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer (1971) characterized 3 alleles of per that shortened (perS; ∼19 h), lengthened (per L; ∼29 h), or abolished (per0) circadian behavioral rhythms. They also showed that transheterozygotes carrying the perS and perL mutations exhibit robust behavioral rhythms with nearly normal periods of ∼23 h, highlighting the semidominant nature of many clock mutants. In this study, per0 flies bearing a doubly mutated per transgene that carries both the per S and perL alleles (per0; per S/L) were analyzed for behavioral and molecular rhythms. Unlike singly mutated versions, the per0;perS/L transgenic flies are arrhythmic in constant dark conditions and exhibit little, if any, entrainment to daily light-dark cycles. In a wildtype per+ background, expression of perS/L abolishes behavioral rhythms, indicating that it functions in a transdominant negative fashion. Biochemical analysis of head extracts revealed that only hyperphosphorylated isoforms of the PERS/L protein are detected throughout a daily cycle, and the levels remain constant. Intriguingly, little if any PERS/L is observed in key pacemaker neurons that control daily activity rhythms, consistent with the notion that hyperphosphorylated isoforms of PER are unstable. Nonetheless, PERS/L is detected in ectopic cells in the brain, in which it exhibits an unusual localization, mainly staining the periphery of the nucleus. These results suggest that posttranslational mechanisms play a key role in limiting the accumulation of PER to specific cells. On a broader scope, our results indicate that the semidominant effects of period-altering alleles observed in trans are not necessarily preserved in the cis-configuration and that novel phenotypes can emerge.

AB - The 1st circadian "clock" gene identified was the X-linked period (per) gene in Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer (1971) characterized 3 alleles of per that shortened (perS; ∼19 h), lengthened (per L; ∼29 h), or abolished (per0) circadian behavioral rhythms. They also showed that transheterozygotes carrying the perS and perL mutations exhibit robust behavioral rhythms with nearly normal periods of ∼23 h, highlighting the semidominant nature of many clock mutants. In this study, per0 flies bearing a doubly mutated per transgene that carries both the per S and perL alleles (per0; per S/L) were analyzed for behavioral and molecular rhythms. Unlike singly mutated versions, the per0;perS/L transgenic flies are arrhythmic in constant dark conditions and exhibit little, if any, entrainment to daily light-dark cycles. In a wildtype per+ background, expression of perS/L abolishes behavioral rhythms, indicating that it functions in a transdominant negative fashion. Biochemical analysis of head extracts revealed that only hyperphosphorylated isoforms of the PERS/L protein are detected throughout a daily cycle, and the levels remain constant. Intriguingly, little if any PERS/L is observed in key pacemaker neurons that control daily activity rhythms, consistent with the notion that hyperphosphorylated isoforms of PER are unstable. Nonetheless, PERS/L is detected in ectopic cells in the brain, in which it exhibits an unusual localization, mainly staining the periphery of the nucleus. These results suggest that posttranslational mechanisms play a key role in limiting the accumulation of PER to specific cells. On a broader scope, our results indicate that the semidominant effects of period-altering alleles observed in trans are not necessarily preserved in the cis-configuration and that novel phenotypes can emerge.

UR - http://www.scopus.com/inward/record.url?scp=36148968850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36148968850&partnerID=8YFLogxK

U2 - 10.1177/0748730407306929

DO - 10.1177/0748730407306929

M3 - Article

VL - 22

SP - 488

EP - 501

JO - Journal of Biological Rhythms

JF - Journal of Biological Rhythms

SN - 0748-7304

IS - 6

ER -