Translocator protein (18 kDa) is involved in primitive erythropoiesis in zebrafish

Abstract

The translocator protein (18 kDa) (TSPO), also known as peripheral-type benzodiazepine receptor, is directly or indirectly associated with many biological processes. Although extensively characterized, the specific function of TSPO during development remains unclear. It has been reported that TSPO is involved in a variety of mechanisms, including cell proliferation, apoptosis, regulation of mitochondrial functions, cholesterol transport and steroidogenesis, and porphyrin transport and heme synthesis. Although the literature has reported a murine knockout model, the experiment did not generate information because of early lethality. We then used the zebrafish model to address the function of tspo during development. Information about spatiotemporal expression showed that tspo has a maternal and a zygotic contribution which, during somatogenesis, seems to be erythroid restricted to the intermediate cell mass. Genetic and pharmacological approaches used to invalidate Tspo function resulted in embryos with specific erythropoietic cell depletion. Although unexpected, this lack of blood cells is independent of the Tspo cholesterol binding site and reveals a new in vivo key role for Tspo during erythropoiesis.

TheArabidopsisMultistress Regulator TSPO Is a Heme Binding Membrane Protein and a Potential Scavenger of Porphyrins via an Autophagy-Dependent Degradation Mechanism

“…TSPO2, a divergent TSPO isoform exclusively expressed in avian and mammalian primitive erythrocytes, is localized to the ER and not the mitochondria, and its expression is tightly correlated with that of hemoglobin genes (Fan et al, 2009;Nakazawa et al, 2009), suggesting a role in heme and hemoprotein accumulation during erythrocyte maturation. In addition, TSPO knockout in zebra fish resulted in embryos with specific erythropoetic cell depletion, and this lack of blood cells was independent of the TSPO function in cholesterol transport and steroidogenesis (Rampon et al, 2009). …”

ATP-dependent Mitochondrial Porphyrin Importer ABCB6 Protects against Phenylhydrazine Toxicity

“…For example, ATP-driven import of such porphyrins such as coproporphyrin III (CP), is completely absent in the mitochondria of Abcb6 Ϫ/Ϫ mice, whereas non-ATP-dependent mitochondrial CP uptake is identical in Abcb6 Ϫ/Ϫ and wild-type mice. Moreover, there is no evident functional up-regulation of other potential mitochondrial porphyrin importers, such as peripheral benzodiazepine receptor (also known as TSPO), 2-oxoglutarate carrier (also known as SLC25a11), the adenine nucleotide translocator (ANT1), and voltage-dependent anion channel, in the absence of Abcb6 (2)(3)(4)(5)(6). In addition, constitutive absence of Abcb6 results in increased expression of genes important for porphyrin biosynthesis (e.g.…”

Current status and future perspectives: TSPO in steroid neuroendocrinology

“…This porphyrinbinding property of TSPO appears highly conserved from bacteria to humans, but the function of this association continues to remain unclear. It was initially proposed that TSPO binds and transports protoporphyrin IX (PPIX), the precursor of heme, into the mitochondria (Wendler et al 2003), a concept that emerged based on TSPO ligands being able to partially rescue cells from porphyrininduced phototoxicity (Ratcliffe & Matthews 1995), and high levels of TSPO expression seen in the bone marrow (Taketani et al 1994, Rampon et al 2009). Although the property of PPIX binding to TSPO remains true, recent studies using Tspo −/− mice and cell lines have established that TSPO is not a porphyrin transporter for heme synthesis .…”