Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

Abstract

BDNF is produced from many transcripts that display distinct subcellular localization, suggesting that spatially restricted effects occur as a function of genetic and physiological regulation. Different BDNF 5′ splice variants give a restricted localization in the cell body or the proximal and distal compartments of dendrites; however, the functional consequences are not known. Silencing individual endogenous transcripts or overexpressing BDNF-GFP transcripts in cultured neurons demonstrated that whereas some transcripts (1 and 4) selectively affected proximal dendrites, others (2C and 6) affected distal dendrites. Moreover, segregation of BDNF transcripts resulted in a highly selective activation of the BDNF TrkB receptor. These studies indicate that spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments.development | neurotrophins | plasticity

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

“…Evidence that different Bdnf transcripts are directed to distinct subcellular compartments following neural activity supports the view that these transcripts serve unique, or only partially overlapping, functions Baj et al, 2012;Baj et al, 2011;Lau et al, 2010;Pattabiraman et al, 2005). In rodents, differential production of Bdnf splice variants has been documented in a number of models of neurological and neuropsychiatric disease and in response to various pharmacological treatments (Dias et al, 2003;Fumagalli et al, 2012;Nair et al, 2007;Zuccato et al, 2001).…”

“…It will also be important to determine the subcellular localization of individual Bdnf transcripts in different brain regions, cell types, and subcellular compartments in vivo. Previous studies in hippocampal cultures demonstrated spatial segregation of Ex1/4 transcripts in proximal dendrites and Ex2/6 transcripts in distal dendrites (Baj et al, 2011). It will be necessary to extend these findings to brain regions containing diverse cell types, such as the HYP, as this may represent another mechanism by which individual Bdnf transcripts may execute diverse functions within a single brain region or neuronal population.…”

BDNF-induced local protein synthesis and synaptic plasticity

“…The CPE-like elements are apparently required for both constitutive and activity-dependent localization of the transcript in dendrites (Oe and Yoneda, 2010). In separated studies, the destination of BDNF mRNA was, ultimately, ruled by the presence of 5 0 UTR exons (Baj et al, 2011;Chiaruttini et al, 2009). The selective localization of several 5 0 UTR splice variants in dendrites was coupled to local TrkB activation and differentially modulates dendritic complexity (Baj et al, 2011).…”

“…In separated studies, the destination of BDNF mRNA was, ultimately, ruled by the presence of 5 0 UTR exons (Baj et al, 2011;Chiaruttini et al, 2009). The selective localization of several 5 0 UTR splice variants in dendrites was coupled to local TrkB activation and differentially modulates dendritic complexity (Baj et al, 2011). Importantly, blocking the dendritic localization of BDNF mRNA in vivo reduced BDNF protein levels in dendrites and resulted in deficits in dendritic spine pruning and enlargement .…”

“…The short 3 0 UTR-carrying mRNAs apparently are restricted to the soma whereas the long 3 0 UTRcontaining mRNAs are also found in dendrites . Nevertheless, BDNF constructs carrying a short 3 0 UTR were shown to be targeted to dendrites in cultured hippocampal neurons (Baj et al, 2011;Chiaruttini et al, 2009;Oe and Yoneda, 2010). The short 3 0 UTR-mediated dendritic targeting of the transcript may rely on the presence of cytoplasmic polyadenylation element (CPE)e like motifs in its sequence (Oe and Yoneda, 2010).…”