Absence of the calcium-binding protein calretinin, not of calbindin D-28k, causes a permanent impairment of murine adult hippocampal neurogenesis

Calretinin (CR) and calbindin D-28k (CB) are cytosolic EF-hand Ca2+-binding proteins and function as Ca2+ buffers affecting the spatiotemporal aspects of Ca2+ transients and possibly also as Ca2+ sensors modulating signaling cascades. In the adult hippocampal circuitry, CR and CB are expressed in specific principal neurons and subsets of interneurons. In addition, CR is transiently expressed within the neurogenic dentate gyrus (DG) niche. CR and CB expression during adult neurogenesis mark critical transition stages, onset of differentiation for CR, and the switch to adult-like connectivity for CB. Absence of either protein during these stages in null-mutant mice may have functional consequences and contribute to some aspects of the identified phenotypes. We report the impact of CR- and CB-deficiency on the proliferation and differentiation of progenitor cells within the subgranular zone (SGZ) neurogenic niche of the DG. Effects were evaluated (1) two and four weeks postnatally, during the transition period of the proliferative matrix to the adult state, and (2) in adult animals (3 months) to trace possible permanent changes in adult neurogenesis. The absence of CB from differentiated DG granule cells has no retrograde effect on the proliferative activity of progenitor cells, nor affects survival or migration/differentiation of newborn neurons in the adult DG including the SGZ. On the contrary, lack of CR from immature early postmitotic granule cells causes an early loss in proliferative capacity of the SGZ that is maintained into adult age, when it has a further impact on the migration/survival of newborn granule cells. The transient CR expression at the onset of adult neurogenesis differentiation may thus have two functions: (1) to serve as a self-maintenance signal for the pool of cells at the same stage of neurogenesis contributing to their survival/differentiation, and (2) it may contribute to retrograde signaling required for maintenance of the progenitor pool

Mitochondria and Lysosomes: Discovering Bonds

In the last decade, the traditional view of lysosomes has been challenged by the recognition that lysosomes are not only degradative organelles, but also metabolic sensors that play a key role in the regulation of metabolism and cell growth. Similarly, mitochondria are now seen as crucial metabolic hubs dictating cell fate decisions, not just ATP-producing machines. Importantly, these functions are generally performed as a coordinate response of distinct organelles that are physically and functionally connected. While the association between mitochondria and the endoplasmic reticulum is well known, a similar interaction between mitochondria and lysosomes is now emerging. This interaction could be required to shuttle amino acids, lipids and ions such as Ca2+ between the two organelles, thereby modulating their metabolic functions. In addition, a tethering complex linking the two organelles has recently been described in yeast, although the mammalian counterpart has yet to be identified. Here, we discuss the implications of these recent findings