Placental Alkaline Phosphatase Isozymes
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Placental alkaline phosphatase (PLAP) is an enzyme encoded by the ALPP gene. Alkaline phosphotases (ALPases) are membrane-associated sialoglycoprotein enzymes, which are normally present at high concentration in syncytiotrophoblasts of the placenta during the third trimester of gestation. PLAP has only been observed in Hominidae (greater apes) and is very different from the ALPases present in lower primates and mammals. The duplication event resulting in the appearance of human-type placental ALPase occurred subsequent to the divergence of the evolutionary lineage leading to the Hylobatidae (lesser apes), but prior to the divergence of the lineage leading to the Hominidae. Also, a number of changes to its promoter region resulted in the subsequent enzyme’s placental specific expression. Human PLAP has several variants of which three are polymorphic, although the importance and possible selective advantages are not yet explored.
Placental ALPase, produced by the fetal side of the placenta, is anchored, in a homodimeric form, to the apical and basal plasma membranes of syncytiotrophoblasts. PLAP expression increases steadily throughout pregnancy until term when it decreases post-partum, and is released in maternal serum starting the second trimester of gestation. The physiological role of placental ALPase is still unclear. As PLAP is Hominidae-specific, studies in other primates might provide insights into higher primate evolution.
Lesser apes and other primates do not have an isoenzyme that resembles human placental phosphatase. The placental enzyme of these species more closely resembles the human liver, bone, and kidney types of ALPase. Recent evidence suggests that the emergence of placental expression of PLAP is prior to the divergence of lineages leading to he Hominidae, but after the lineages leading to lesser apes, like gibbon. It is unclear, however, if the duplication occurred within this timeframe or only the change in regulatory mechanism. An old world monkey lung-specific ALPase could be the product of the same duplication event, but diverged in expression within the two lineages. A comparison of the placental ALP’s 5’ flanking sequence (up to -540) with that of intestinal ALP gene shows many deletion/substitutions which could result in tissue-specific expression changes.
All humans express PLAP. Unlike most ALPases, which are highly conserved, the PLAP locus is variable, with three polymorphic and at least 15 rare variants documented. Three of these alleles, named Pl1, Pl2 and Pl3, give rise to six common electrophoretic phenotypes characterized by different enzyme activities. PI1 and PI2 display differential mRNA expression linked to a sequence variation within their promoter regions. The relevance of these variants is not well studied.
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