Amelogenins: Multifaceted Proteins for Dental and Bone Formation and Repair

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Potential Role of Adaptor Protein Complex-3 (Ap-3) In Amelogenesis

Pp. 56-63 (8)

Jason L. Shapiro, Rodrigo S. Lacruz, Steven J. Brookes, S. Petter Lyngstadaas and Michael L. Paine

Abstract

As identified using in vitro methodologies, the enamel matrix proteins (EMPs) bind a class of proteins called lysosomal associated membrane proteins (LAMPs), whose members are LAMP1, LAMP2 and CD63/LAMP3. LAMPs are transmembrane proteins present in the plasma membrane, and all three directly interact with the AP-3 complex to initiate receptor-mediated endocytosis. In yeast, AP-3 associated endocytosis is clathrin-independent, while in higher organisms the requirement of clathrin is unclear. AP-3 is a protein complex with four subunits referred to as β, δ, μ and σ Three other adaptor protein complexes (AP-1, AP-2 and AP-4), each having four similar but unique subunits, are also involved with endocytosis and are either clathrin-dependent (AP-1 and AP-2) or clathrin-independent (AP-4). Only AP-3 interacts directly with plasma membrane-bound LAMPs. It is likely that endocytosis of the degraded EMPs plays a significant role in enamel maturation, and if so, AP-3 dysfunction may result in enamel abnormalities. We have initiated in vivo studies to better define the dental phenotype in a strain of mice null for the β subunit of AP-3 (coded by the AP3B1 gene), which results in the loss of AP-3 function. The driving hypothesis of future studies is that “failure of normal ameloblast endocytosis of the degraded EMPs during enamel maturation results in functionally inferior enamel more prone to dental disease”. The question we expect to answer from these mice studies is whether the receptor-mediated AP-3 endocytotic pathway is a prominent feature of amelogenesis. This chapter discusses the potential role of AP-3 mediated endocytosis in amelogenesis and describes animal experimental models that could be used to examine such a relationship.

Keywords:

Adaptor Protein Complex, Amelogenesis, Enamel Formation, Endocytosis, Hermansky-Pudlak Syndrome, Pearl Mice

Affiliation:

University of Southern California School of Dentistry, Center for Craniofacial Molecular Biology, 2250 Alcazar Street, CSA room 103, Los Angeles, CA 90033, USA.