Rab11 endosomes regulate both the dendrite morphology and the specific positioning of dendritic proteins

ARTUR DE LA VILLARMOIS E; CONDE C; ROZÉS-SALVADOR, VICTORIA; PÉREZ MF; SIRI SO; GHERSI MS

San Diego

Congreso; Neuroscience 2018; 2018

Society for Neuroscience

The correct development of the dendritic arbor requires a properspatiotemporal distribution of the elements of the secretory and endocyticpathways, as well as a dynamic and tightly regulated communication betweenthem. One of the main players in these processes is the Rab family of smallGTPases. The members of this family of proteins not only regulate endocytictraffcking but also act as specific markers for different types of endosomes.Emerging evidence shows that Rab11 play a role in several neuronal processesis required for the proper functioning of the growth cone and regulation of thesynapse architecture. However, less is known about the specific function ofRab11 in the development of the dendritic arbor. Thus, we have focused ourwork on characterizing the role of the Rab11-positive (Rab11+) recyclingendosomes (REs) during neuronal development using a model of primaryculture of embryonic rat hippocampal (HP) neurons. Furthermore, we aimed tocharacterize the functional role of Rab11 in HP synaptic plasticity and itscorrelate in an HP-dependent behavior in adult rats. First, we determined theendogenous localization of the Rab11+ REs at different stages of the neuronaldevelopment in vitro. The immunostaining experiments showed that duringthe first 24 hours and up to 3 days in vitro (DIV), Rab11 is mainly distributed inthe neurites tips of the minor processes and redistributed to a juxtanuclearposition at later stages. Moreover, suppression of Rab11 resulted in ashortening of the main neurite and increased number of dendritic branches.These alterations were accompanied by a significant miss-distribution ofdendritic proteins, which were found not only in dendrites but also in axons.For example, we observed that the reduction of Rab11 expression selectivelyalters the traffic and delivery to the plasma membrane of Transferrin receptor(TfR) and AMPA receptor subunit (GluR1). In addition, the in vivo Rab11suppression by injecting animals with lentiviral particles in the CA1 region ledto decrease sensitivity to induce HP long-term potentiation and to a reducedperformance in memory-related behaviors. Taken together, our experimentalresults indicate that Rab11 follow a spatial pattern of distribution that changes with the neuronal stage development. The specific REs localization at each stage seems to be a requirement, not only for the elongation and branching of dendritic processes at early stages but also to control key aspects of neuronal development as maturation and proper function of the neuronal dendritictree. At later stages, in mature neurons, Rab11 would play a role in themaintenance of synaptic transmission and in memory formation