Unfolding the Future - The Functional Fold: Amyloid Structures in Nature - page 162

those studied did indeed release monomeric hormone on dilution.
Further, the authors established that the released monomers were
indeed functional. This highlights the continuing need to reconsider
and reinvestigate widespread beliefs in the area of amyloid research.
It is also interesting to note that the first paper indicating the
distinct molecular organization and possible crystalline structure
in secretory granules was published in 1966

12

but a considerable

time has lapsed before Maji ., provided sufficient evidence, using

a substantial number of complementary techniques (see Section
10.2), for the structures to be accepted as being in an amyloid form.
In a second “storage” related function

et al

cytoplasmic poly-
adenylation element binding protein (ApCPEB) was shown to be
able to form an amyloidogenic self-sustaining multimer, which
appears to contribute to long-term synaptic changes associated with
memory storage.

Aplysia

10

This potential function was first proposed by the
same authors in 2003 after observing that ApCPEB had properties
consistent with it being a prion-like protein when fused to a reporter
protein in yeast.

13

Further, in their original paper the authors
highlighted that like the fungal prion protein HetS (see Chapter 6), it
is the dominant self-perpetuating form that is associated with a gain
of function (biochemical activity in the case of ApCPEB). The lack
of direct evidence in neurons at that time necessitated substantial
additional research to, in the first instance establish that in Aplysia

sensory neurons, ApCPEB does indeed exist in a monomeric and
multimeric state. Further, to establish the functional link the
authors showed that the prion-like conversion from a monomeric
to a multimeric form was modulated by synaptic stimulation and
that ApCPEB is active in the multimeric prion-like state. Finally
the authors utilized an antibody that preferentially binds to the
multimeric form and diminishes its activity in order to reach the
fascinating conclusions that the multimeric amyloid form of Aplysia
CPEB is involved in long-term stabilization of activity-dependent
change in synaptic efficacy.

10.4 Relevance to the Field of

Pathogenic Amyloid

As has been highlighted in many of the previous chapters, amyloid
fibrils are notorious for their association with debilitating and