編者按：隨著生物學的認識,，細胞內許多物質的功能都不象以前的那么簡單,，許多物質扮演著多重角色，即在我們看來有時是有利的,，有時是不利的一面,。如許多凋亡蛋白，在執(zhí)行細胞凋亡程序,，但同時它在細胞的分化和發(fā)育中,，以及細胞的自我保護中起著十分重要的作用，誰又能忽視呢,？如果沒有凋亡,，細胞群體在接觸損傷以后，一個細胞的損傷,，其內容物可能會導致整個群體崩潰,！而正因為凋亡，使細胞內損傷性內容物（蛋白酶）得以不釋放,，從而間接抑制了更大可能的傷害,。而且在我們看來，損傷與保護是一個相反過程,，其實同樣是一個反饋過程,！只有相反方向的因素綜合，才能保證系統(tǒng)的穩(wěn)定性,。這便是生命的有趣性和秘密?。╞ioon按）
Prions are famous evildoers. These misfolded proteins cause deadly neurodegenerative diseases, including "mad cow disease," in mammals. Now, researchers may have discovered the first helpful function of a prionlike protein: the formation of long-term memories.
Switchover. In yeast cells, CPEB can flip between an active prionlike form (blue) and an inactive form (white). Such changes in neurons may contribute to memory.
CREDIT: K. SI ET AL., CELL 115, 879 (2003)
A team led by neuroscientist Eric Kandel and postdoc Kausik Si at Columbia University College of Physicians and Surgeons in New York City has been investigating the mechanisms of memory in neurons of the sea slug Aplysia. The researchers had found that repeatedly spritzing one branch of a sensory neuron with the neurotransmitter serotonin creates memory-forming proteins within that one branch alone. But the neuron appeared to be sending the messenger RNAs (mRNAs) needed to synthesize the required memory-forming proteins to all its branches. So the serotonin input apparently somehow marked the affected branches so that only they could use the mRNAs.
Si suspected that a protein called CPEB could be the mark because it activates mRNAs, chemically preparing them to be translated into proteins, and because it springs into action when neurons are stimulated. Indeed, Si soon found that blocking CPEB production stymied the cellular changes that underlie long-term memory.
Still, one mystery remained. Because most proteins degrade within hours, it was unclear how CPEB could maintain changes within the nerve terminal that last many years, as some memories do. But then Si noticed that one end of CPEB carries a prionlike sequence. Prions are proteins with two possible conformational states, one of which is soluble whereas the other is insoluble and long-lasting in cells. The insoluble form is thought to turn the soluble form into its insoluble state when the two forms come in contact. That's the mechanism suspected in mammalian prion diseases, and another set of experiments revealed that CPEB acts like a prion, at least in yeast. The researchers, who reported their findings in the 26 December issue of Cell, speculate that small amounts of prion CPEB, produced in a stimulated nerve ending, may convert many more inactive proteins into active forms. The active forms would help activate mRNA and stabilize the synapse, forming the memory.
The work has led to the radically new notion--which is far from proven--that prionlike changes in protein shape may be a key molecular event in the formation of stable memories, says neuroscientist Solomon Snyder of Johns Hopkins University in Baltimore, Maryland. "It's the first truly novel concept about a molecular mechanism for learning and memory in perhaps 30 years."
--INGRID WICKELGREN
Related sites
The Kandel lab
More about prions and the diseases they cause
