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Myosin V is the rate-determinative step in Xenopus melanophore aggregation
Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

In Xenopus melanophores, melatonin induce melanosome aggregation via activation of its receptor Mel1c, coupled to inhibitory G proteins, adenylate cyclase deactivation, cyclic adenosine 3':5'-monophosphate (cAMP) decrease, protein kinase A inhibition, protein phophatase 2A activation, and serine/threonine dephosphorylations. Myosin V is the motor protein responsible for transporting melanosomes along actin filaments. Myosin V has been demonstrated to be necessary for melanosome dispersion and to keep the dispersed state. We have previously shown that melatonin induce activation of phosphoinositide-3 kinase, mitogen-activated protein kinase and tyrosine phosphorylation of a 280-kDa protein. Here we characterize the kinetics of latrunculin A-induced aggregation, and show that latrunculin A aggregate melanophores with the same kinetics as melatonin. This indicates that the downstream mechanisms might be similar although their primary targets in the cells are totally different. We suggest that both drugs act by inhibiting myosin V, the rate-determinative step for melanosome aggregation. Our data suggest that dynein is not up regulated during aggregation, as previously suggested by others,

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-84527OAI: oai:DiVA.org:liu-84527DiVA, id: diva2:560090
Tillgänglig från: 2012-10-11 Skapad: 2012-10-11 Senast uppdaterad: 2012-10-12Bibliografiskt granskad
Ingår i avhandling
1. Melanophore signaling: regulation and application
Öppna denna publikation i ny flik eller fönster >>Melanophore signaling: regulation and application
2003 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Melanophores are pigment-containing cells responsible for quick physiological color changes in lower vertebrates due to redistribution of melanosomes, pigment granules. We have studied melanophores from African clawed frog, Xenopus laevis. Classically, melanosomes can be stimulated to aggregate in the cell center by the hormone melatonin via a process involving activation of the inhibitory Gi/o protein and inhibition of adenylate cyclase/cAMP/protein kinase A pathway. In addition, tyrosine phosphorylations have been shown to be crucial for aggregation. In this thesis, we demonstrate that mitogen-activated protein kinase (MAPK) are activated and phosphoinositol 3-kinase (PI3-K) are involved in melatonininduced aggregation. Inhibition of MAPK kinase or PI3-K inhibits MAPK activation, tyrosine phosphorylation of a 280-kDa protein and aggregation. Further, PI3-K inhibition is less dramatic in fish Labrus melanophores. Together with findings that phosphodiesterase (PDE) 4 and/or PDE2 are involved in keeping the aggregated state in Xenopus, we suggest that active PI3-K via MAPK stimulates PDE, thus lowering cAMP. We also use latrunculin A to induce aggregation via disruption of actin filaments. Kinetic studies indicate that melatonin and latrunculin share final downstream target, possibly inactivate myosin-V leading to melanosome aggregation. As biosensor application, a new computer screen assisted technique suitable for bioassays is demonstrated using melanophores to monitor kinetic responses of melanosome movement and blood plasma sample detection of the asthma drug and ß2 adrenergic agonist formoterol. We also used melanophores to examine the efficacy of enantiomers of formoterol. We confirm that (R;R)-formoterol is more potent than (S;S)-formoterol, in guinea pig tracheal ring preparations, cultured melanophores, and radioligand binding on COS-7 cells, but demonstrate and calculate that (S;S)-formoterol has more efficacy than previously described. Characterization of melanophores are important for biosensor applications, i e to understand mechanisms of drugs, and will probably also increase the knowledge of cell signaling in other cell systems.

Ort, förlag, år, upplaga, sidor
Linköping: Linköpings universitet, 2003. s. 64
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 799
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-27457 (URN)12110 (Lokalt ID)91-7373-485-3 (ISBN)12110 (Arkivnummer)12110 (OAI)
Disputation
2003-09-05, Aulan, Administrationshuset, Hälsouniversitet, Linköping, 13:00 (Svenska)
Opponent
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2012-10-12Bibliografiskt granskad

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Andersson, Tony P. M.Lundström, IngemarSvensson, Samuel P. S.

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