Figure 12.

Schematic model of TRIP8b function in hippocampal CA1 neurons. A, Sample CA1 pyramidal neuron. B, Schematic drawing of CA1 pyramidal neuron soma (top) and distal dendrite (bottom). HCN channels (green) are expressed in endoplasmic reticulum (ER), assembled as tetramers, sorted into Golgi (1), and then trafficked into dendrites (2) without requiring TRIP8b (red). In distal dendrites, TRIP8b facilitates targeting of HCN channels to plasma membranes by unknown mechanisms (3). C, Schematic of CA1 pyramidal neuron distal dendrite showing TRIP8b (red) colocalized with HCN channels (green) and favoring trafficking from an endocytic recycling compartment (ERC) to plasma membrane (thick arrow) (PM), and limiting trafficking to multivesicular bodies/lysosomes. D, In the TRIP8b^−/− mice, HCN channels are not efficiently targeted to plasma membrane resulting in increased targeting to multivesicular bodies and degradation by lysosomes (thick arrow).