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

CONDE, CECILIA; SEBASTIÁN OMAR SIRI; ROZÉS-SALVADOR, VICTORIA; DE LA VILLARMOIS, EMILCE ARTUR

san Diego, CA

Congreso; 2018 Neuroscience Meeting; 2018

Society for Neuroscience

The correct development of the dendritic arbor requires a proper spatiotemporaldistribution of the elements of the secretory and endocytic pathways, as wellas a dynamic and tightly regulated communication between them. One of the main players in theseprocesses is the Rab family ofsmall GTPases. The members of this family of proteins not only regulate endocytic trafficking but also act as specific markers for different types ofendosomes. Emerging evidence shows that Rab11 play a role in several neuronal processes is requiredfor the proper functioning of the growth cone and regulation of the synapse architecture.However, less is known about the specific function of Rab11 in the development of the dendriticarbor. Thus, we have focused our work on characterizing the role of the Rab11-positive (Rab11+)recycling endosomes (REs) during neuronal development using a model of primary culture ofembryonic rat hippocampal (HP) neurons. Furthermore, we aimed to characterize thefunctional role of Rab11 in HP synaptic plasticity and its correlate in an HP-dependent behaviorin adult rats. First, we determined the endogenous localization of the Rab11+ REs at different stagesof the neuronal development in vitro. The immunostaining experiments showed that during thefirst 24 hours andup to 3 days in vitro (DIV), Rab11 is mainly distributed in the neurites tipsof the minorprocesses and redistributed to a juxtanuclear position at later stages.Moreover, suppression of Rab11 resulted in a shortening of the main neurite and increased number of dendriticbranches. These alterations were accompanied by a significant miss-distribution ofdendritic proteins, which were found not only in dendrites but also in axons. For example, weobserved that the reduction of Rab11 expression selectively alters the traffic and delivery tothe plasma membrane of Transferrin receptor (TfR) and AMPA receptor subunit (GluR1). In addition,the in vivo Rab11 suppression by injecting animals with lentiviral particles in the CA1region led to decrease sensitivity to induce HP long-term potentiation and to a reducedperformance in memory-related behaviors. Taken together, our experimental results indicatethat Rab11 follow a spatial pattern of distribution that changes with the neuronal stagedevelopment. The specific REs localization at each stage seems to be a requirement, not only for theelongation and branching of dendritic processes at early stages but also to control keyaspects of neuronal development as maturation and proper function of the neuronal dendritic tree. Atlater stages, in mature neurons, Rab11 would play a role in the maintenance of synaptictransmission and in memory formation