Cell derived hierarchical assembly of a novel phosphophoryn-based biomaterial.
Phosphophoryn (PP) is an acidic phosphoprotein belonging to the small integrin-bindingligand N-linked glycoprotein (SIBLING) protein family. PP is highly phosphorylated with approximately 200 phosphates per molecule and has a high affinity for calcium. The aim of this manuscript is to demonstrate that PP has the ability to self-assemble when it is overexpressed in a mammalian cell in the presence of calcium. Our data show that when PP is overexpressed using an adenovirus, the self-assembly occurs in the endoplasmic reticulum (ER) which contains high calcium concentration. We hypothesize that the physicochemical properties of the highly phosphorylated state and acidic nature of PP are playing an important role in its assembly in the ER. It appears that when a critical concentration of PP is reached, the assembly is then favored and facilitated. This self-assembly could be due to several factors. (1) The ER provides an ideal environment for this phenomenon to occur, since the ER environment usually promotes aggregation [Stevens and Argon: Semin Cell Dev Biol 1999;10:443-454]. (2) In addition to PP's physicochemical properties, the unfolded protein response could also be playing a role in this self-assembly [Schroder and Kaufman: Mutat Res 2005;569:29-63]. Unfolded protein response could be activated by a broad spectrum of insults that result in protein misfolding and ultimately blocking of the protein synthesis progression to the Golgi apparatus resulting in an accumulation of the protein in the ER. In summary, our data show that PP has the ability to self-assemble in a hierarchical manner.
Li
Jinhua
J
Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa. 15261-1964, USA.
Olton
Dana
D
Lee
Donghyun
D
Kumta
Prashant N
PN
Sfeir
Charles
C
D000256:Adenoviridae / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000378:metabolism*; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*
D010750:Phosphoproteins; C017630:phosphophoryn