编者按：随着生物学的认识，细胞内许多物质的功能都不象以前的那么简单，许多物质扮演着多重角色，即在我们看来有时是有利的，有时是不利的一面。如许多凋亡蛋白，在执行细胞凋亡程序，但同时它在细胞的分化和发育中，以及细胞的自我保护中起着十分重要的作用，谁又能忽视呢？如果没有凋亡，细胞群体在接触损伤以后，一个细胞的损伤，其内容物可能会导致整个群体崩溃！而正因为凋亡，使细胞内损伤性内容物（蛋白酶）得以不释放，从而间接抑制了更大可能的伤害。而且在我们看来，损伤与保护是一个相反过程，其实同样是一个反馈过程！只有相反方向的因素综合，才能保证系统的稳定性。这便是生命的有趣性和秘密！（bioon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
