| 1. |
- Johnsson, Anna-Karin, 1980-, et al.
(författare)
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Microtubule-dependent localization of profilin I mRNA to actin polymerization sites in serum-stimulated cells
- 2010
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Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 89:5, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- Specific localization of messenger RNA (mRNA) appears to be a general mechanism to accumulate certain proteins to subcellular compartments for participation in local processes, thereby maintaining cell polarity under strict spatiotemporal control. Transportation of mRNA with associated protein components (RNP granules) by the actin microfilament or the microtubule systems is one important mechanism to achieve this locally distributed protein production. Here we provide evidence for a microtubule-dependent localization of mRNA encoding the actin regulatory protein profilin to sites in mouse embryonic fibroblasts, which express enhanced actin polymerization.
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| 2. |
- Johnsson, Anna-Karin, 1980-
(författare)
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Profilin and actin localizes to Synaptotagmin-induced filopodia
- 2007
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Annan publikation (populärvet., debatt m.m.)abstract
- We are interested in the dynamics of the microfilament system at the leading edge. Our main focus is to explore how profilin:actin is transported to actin polymer forming sites at the inner leaflet of the plasma membrane. As a model system to study this process we are overexpressing synaptotagmin 1 in mammalian cells. This leads to a dramatic change in cell morphology with numerous oversized filopodia beeing formed. In addition to using this effect as a model system we are also interested in characterizing the mechanism responsible for this process. We have seen that the synaptotagmin 1 induced filopodia stain positively for profilin and actin and that they are enriched in the phosphatidylinositol lipid PIP2. Through cotransfection with a dominant negative form of Cdc42 we have indications that the formation of these filopodia is dependent on this small Rho GTPase.ASCB/ECF-möte i Dijon 27-30 juni 2007
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| 3. |
- Johnsson, Anna-Karin, 1980-, et al.
(författare)
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Synaptotagmin 1 causes phosphatidyl inositol lipid-dependent actin remodeling in cultured non-neuronal and neuronal cells
- 2012
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 318:2, s. 114-126
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Tidskriftsartikel (refereegranskat)abstract
- Here we demonstrate that a dramatic actin polymerizing activity caused by ectopic expression of the synaptic vesicle protein synaptotagmin 1 that results in extensive filopodia formation is due to the presence of a lysine rich sequence motif immediately at the cytoplasmic side of the transmembrane domain of the protein. This polybasic sequence interacts with anionic phospholipids in vitro, and, consequently, the actin remodeling caused by this sequence is interfered with by expression of a phosphatidyl inositol (4,5)-bisphosphate (PIP2)-targeted phosphatase, suggesting that it intervenes with the function of PIP2-binding actin control proteins. The activity drastically alters the behavior of a range of cultured cells including the neuroblastoma cell line SH-SY5Y and primary cortical mouse neurons, and, since the sequence is conserved also in synaptotagmin 2, it may reflect an important fine-tuning role for these two proteins during synaptic vesicle fusion and neurotransmitter release.
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| 4. |
- Johnsson, Anna-Karin, 1980-
(författare)
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The Actin Filament System : Its Involvement in Cell Migration and Neurotransmitter Release
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The microfilament system consists of actin filaments as the major component and is regulated by a number of actin binding proteins. It is juxtaposed to the plasma membrane where it forms a dense cortical weave from where it pervades into the cell interior. This filament system has multiple roles and participates in virtually all motile processes where its dynamic activities depend on receptor mediated signaling leading to constant polymerizations and depolymerizations. These activities are now also known to affect gene regulation. This thesis discusses these dynamic reorganizations of the microfilament system and how components are supplied to support these motile processes. The focus is on profilin/profilin:actin, actin polymerization and the localization of the transcripts of these proteins.The localization of profilin mRNA was examined in relation to the distribution of β-actin mRNA using fluorescent in situ hybridization. It was concluded that both these mRNAs localize to sites of massive actin polymerization called dorsal ruffles albeit the data obtained suggests that this localization must be dependent on distinct mechanisms. Additionally signal transduction and cell motility was studied after depleting the two profilin isoforms 1 and 2. The activity of the transcription factor SRF is known to be coupled to microfilament system dynamics via the cofactor MAL which binds to actin monomers and is released upon receptor mediated actin polymerization. Depletion of profilin was seen to influence SRF dependent signaling, most likely because the lack of profilin enables more MAL to bind actin monomers thereby preventing SRF dependent transcription. Finally, it was also investigated how the synaptic vesicle protein synaptotagmin 1 which is involved in exocytosis, has a role in actin polymerization. This protein has previously been described to cause filopodia formation when ectopically expressed. A polybasic sequence motif was identified as the effector sequence for this activity and it was established that this sequence interacts with anionic lipids. It is also discussed how this sequence could have a role in neurotransmitter release and actin polymerization in the nerve synapse.
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