Related Experiment Video
Updated: May 2, 2026
09:07
Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
13.1K
The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development.
Julia C Geiger1, Joanna Lipka2, Inmaculada Segura3
1Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany; Focus Program Translational Neurosciences (FTN), University of Mainz, 55131 Mainz, Germany.
Developmental Cell
|March 1, 2014
Summary
Glutamate receptor interacting protein 1 (GRIP1) is crucial for dendrite development. Its interaction with 14-3-3 proteins regulates neuronal cargo transport by controlling kinesin-1 motor attachment.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neuronal development relies on regulated cargo transport.
- The function of PDZ scaffolding proteins in this process is not fully understood.
Purpose of the Study:
- To investigate the role of glutamate receptor interacting protein 1 (GRIP1) in neuronal development and cargo trafficking.
- To elucidate the mechanism by which GRIP1 functions as an adaptor protein.
Main Methods:
- Genetic deletion in mice to assess GRIP1 function.
- Identification of protein-protein interactions using biochemical assays.
- Analysis of a point mutation affecting GRIP1 function in transgenic mice.
Main Results:
- GRIP1 is essential for dendrite development in mice.
- GRIP1 interacts with 14-3-3 proteins, regulating its function as an adaptor.
- 14-3-3 binding to GRIP1 is phospho-dependent and detaches it from kinesin-1, controlling cargo transport.
- A specific mutation in GRIP1 impairs dendritic development.
Conclusions:
- GRIP1 plays a critical regulatory role in microtubule-based transport during neuronal development.
- 14-3-3 proteins are crucial for controlling kinesin-1 motor attachment to cargo adaptors like GRIP1.
Related Concept Videos
01:33Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
01:32Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
01:12Clathrin Coated Vesicles
8.1K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
8.1K
01:45ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
01:26Transport Across the Golgi
5.2K
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
5.2K
01:45Vesicular Tubular Clusters
2.4K
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
2.4K