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

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

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 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 endocytictracking but also act as specific markers for different types of endosomes.Emerging evidence shows that Rab11 plays 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 itscorrelation in an HP-dependent behavior in adult rats. First, we determined theendogenous localization of the Rab11+ REs at different stages of neuronaldevelopment in vitro. The immunostaining experiments showed that duringthe rst 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 an 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 trac and delivery to the plasma membrane of the 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 reducedperformance in memory-related behaviors. Taken together, our experimentalresults indicate that Rab11 follows a spatial pattern of distribution that changeswith the neuronal stage development. The specific REs localization at eachstage seems to be a requirement, not only for the elongation and branching ofdendritic processes at early stages but also to control key aspects of neuronaldevelopment such 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