NF1 tumor suppressor mRNA is targeted to the cell-cell contact zone in Ca(2+)-induced keratinocyte differentiation.
We have previously shown that NF1 (type 1 neurofibromatosis) p21ras GTPase-activating tumor suppressor protein undergoes major relocalization during the formation of cell-cell junctions in differentiating keratinocytes in vitro. This prompted us to study the distribution of NF1 mRNA under the same conditions by in situ hybridization. In differentiating keratinocytes, the NF1 mRNA signal intensified within the cell cytoplasm within the first 0.5 to 2 hours after induction of cellular differentiation. First, the hybridization signal was evenly distributed throughout the cytoplasm. Subsequently, NF1 mRNA was gradually polarized to the cellular periphery at the side of cell-cell junctions and finally disappeared. Reappearance of NF1 mRNA was found in migrating keratinocytes forming a bilayered culture. Disruption of microfibrillar cytoskeleton, but not microtubules, caused a marked change in the subcellular distribution of NF1 mRNA. This data may suggest that intact actin microfilaments are essential for transport of NF1 mRNA to the cell periphery. This is the first study demonstrating that NF1, or any tumor suppressor mRNA, belongs to a rare group of mRNAs not targeted to free polysomes or ribosomes of the rough endoplasmic reticulum. This finding recognizes a potential way for post-transcriptional modification of NF1 expression.
Ylä-Outinen
Heli
H
Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.
Koivunen
Jussi
J
Nissinen
Marja
M
Björkstrand
Ann-Sofi
AS
Paloniemi
Marja
M
Korkiamäki
Timo
T
Peltonen
Sirkku
S
Karvonen
Seija-Liisa
SL
Peltonen
Juha
J
D000328:Adult; D000368:Aged; D002118:Calcium / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger; D015638:Cytochalasin D; D002118:Calcium