Developmental expression of heterotrimeric G-proteins in the murine cerebellar cortex.

We utilized the murine cerebellum to analyze the expression of G-proteins during vertebrate neural differentiation. Combining reverse transcription-polymerase chain reaction and immunocytochemistry, we monitored the expression and cellular localization, within the nascent cerebellar cortex, of G-proteins subunits known to mediate signal transduction in the adult cerebellum. The mRNAs encoding subunits Galphaq, Galphao, Galphai-2, and Galphaz are expressed in the cerebellar anlage at least from embryonic day 14 onward, and relative levels of these mRNAs do not change appreciably from E14 to adulthood. Galphao, Galphaz, and Galphai-2 could be localized to granule cell neuroblasts and postmigratory, mature granule cells, but not to early postmitotic, premigratory, and migrating granule neurons. All of the Galpha subunits analyzed could also be localized to the cell somata of postmitotic Purkinje neurons, irrespective of age. In contrast, Purkinje cell dendrites stained for Galphao only up to postnatal day 8, dendritic immunoreactivity for Galphaz increased during dendritogenesis, and appreciable levels of Galphai-2 and Galphaq were seen in Purkinje cell dendrites only transiently during the 2nd and 3rd postnatal week. Of the G-beta and -gamma subunits analyzed (beta1, beta2, gamma2, gamma3, gamma5, and gamma7), only expression of gamma3 varied with development. It could be localized to Purkinje cell somata and dendrites in early postnatal, but not in adult animals. These changes in the cellular distribution and subcellular segregation of G-proteins are correlated to tangible aspects of cerebellar cortical histogenesis and suggest a role for G-protein-mediated signaling in their mechanistic implementation.

Biology of tartrate-resistant acid phosphatase.

Tartrate-resistant acid phosphatase (TRAP) is a member of the ubiquitously expressed enzyme family of the acid phosphatases. Nearly 30 years ago, TRAP became known to hematologists as cytochemical marker enzyme of hairy cell leukemia. Physiologically, TRAP is primarily a cytochemical marker of macrophages, osteoclasts and dendritic cells. TRAP is localized intracellularly in the lysosomal compartment. Recent data suggest also secretion of TRAP by some cell types, in particular by osteoclasts. Human, mouse and rat TRAP are biochemically well characterized. While the complete genomic sequence of TRAP has been elucidated, only limited information on the genetic details of the gene and its regulation is available. It appears that the intracellular iron content is involved in the regulation of the enzyme. The physiological substrates for this enzyme have not been identified yet and consequently the functional role of TRAP remains completely unknown, though some hypotheses have been forwarded, e.g. involvement in bone resorption and iron homeostasis (transport, metabolism). Taken together, research on the biology of TRAP has been intensive and has led to considerable progress on a number of fronts, including the cloning of the gene. Further studies are, however, still required to determine the role of TRAP in vivo.