Proliferative arrest of neural cells induces prion protein synthesis, nanotube formation, and cell-to-cell contacts.
Host prion protein (PrP) is most abundant in neurons where its functions are unclear. PrP mRNA transcripts accumulate at key developmental times linked to cell division arrest and terminal differentiation. We sought to find if proliferative arrest was sufficient to cause an increase in PrP in developing neurons. Rat neuronal precursor cells transduced with the temperature sensitive SV-40 T antigen just before terminal differentiation (permissive at 33 degrees C but not at 37.5 degrees C) were analyzed. By 2 days, T antigen was decreased in all cells at 37.5 degrees C, with few DNA synthesizing (BrdU+) cells. Proliferative arrest induced by 37.5 degrees C yielded a fourfold PrP increase. When combined with reduced serum, a sevenfold increase was found. Within 2 days additional neuritic processes with abundant plasma membrane PrP connected many cells. PrP also concentrated between apposed stationary cells, and on extending growth cones and their filopodia. Stationary cells were maintained for 30 days in their original plate, and they reverted to a proliferating low PrP state at 33 degrees C. Ultrastructural studies confirmed increased nanotubes and adherent junctions between high PrP cells. Additionally, some cells shared cytoplasm and these apparently open regions are likely conduits for the exchange of organelles and viruses that have been observed in living cells. Thus PrP is associated with dynamic recognition and contact functions, and may be involved in the transient formation of neural syncytia at key times in embryogenesis. This system can be used to identify drugs that inhibit the transport and spread of infectious CJD particles through the nervous system.
Miyazawa
Kohtaro
K
Yale Medical School, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Emmerling
Kaitlin
K
Manuelidis
Laura
L
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D043942:Nanotubes; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011328:Prions / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats
D011328:Prions