Kalirin Interacts with TRAPP and Regulates Rab11 and Endosomal Recycling
Open Access
- 4 May 2020
- Vol. 9 (5), 1132
- https://doi.org/10.3390/cells9051132
Abstract
Coordinated actions of Rab and Rho are necessary for numerous essential cellular processes ranging from vesicle budding to whole cell movement. How Rab and Rho are choreographed is poorly understood. Here, we report a protein complex comprised of kalirin, a Rho guanine nucleotide exchange factor (GEF) activating Rac1, and RabGEF transport protein particle (TRAPP). Kalirin was identified in a mass spectrometry analysis of proteins precipitated by trappc4 and detected on membranous organelles containing trappc4. Acute knockdown of kalirin did not affect trappc4, but significantly reduced overall and membrane-bound levels of trappc9, which specifies TRAPP toward activating Rab11. Trappc9 deficiency led to elevated expression of kalirin in neurons. Co-localization of kalirin and Rab11 occurred at a low frequency in NRK cells under steady state and was enhanced upon expressing an inactive Rab11 mutant to prohibit the dissociation of Rab11 from the kalirin-TRAPP complex. The small RNA-mediated depletion of kalirin diminished activities in cellular membranes for activating Rab11 and resulted in a shift in size of Rab11 positive structures from small to larger ones and tubulation of recycling endosomes. Our study suggests that kalirin and TRAPP form a dual GEF complex to choreograph actions of Rab11 and Rac1 at recycling endosomes.This publication has 39 references indexed in Scilit:
- TRAPP complexes in membrane traffic: convergence through a common RabNature Reviews Molecular Cell Biology, 2010
- Disruption of Rab11 activity in a knock-in mouse model of Huntington's diseaseNeurobiology of Disease, 2009
- The Arp2/3 Activator WASH Controls the Fission of Endosomes through a Large Multiprotein ComplexDevelopmental Cell, 2009
- Mutant Huntingtin Impairs Vesicle Formation from Recycling Endosomes by Interfering with Rab11 ActivityMolecular and Cellular Biology, 2009
- Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic SpinesNeuron, 2007
- The Rab5 Activator ALS2/alsin Acts as a Novel Rac1 Effector through Rac1-activated EndocytosisOnline Journal of Public Health Informatics, 2007
- Plasticity-Induced Growth of Dendritic Spines by Exocytic Trafficking from Recycling EndosomesNeuron, 2006
- Kalirin: A Dual Rho Guanine Nucleotide Exchange Factor That Is So Much More Than the Sum of Its Many PartsThe Neuroscientist, 2005
- Endocytic recyclingNature Reviews Molecular Cell Biology, 2004
- An Isoform of Kalirin, a Brain-specific GDP/GTP Exchange Factor, Is Enriched in the Postsynaptic Density FractionOnline Journal of Public Health Informatics, 2000