User:Robiso22/sandbox

Role of GRIP1 in neuron morphology and cargo transport
Neuron morphology, development, and maintenance are dependent on the expression of GRIP1 in the cell. Data is currently lacking on the exact mechanisms and functionality of GRIP1, but it has been shown what some of the results are when GRIP1 is altered.

GRIP1 is vitally important in initial development as knock out experiments in mouse models result in skin blisters and embryonic lethality. In teenage and adult mouse models, disabling mutations like transfecton or dominant negatives in GRIP1 can cause up to 75% loss in “primary, secondary, and higher-order” dendrites in developing neurons.

Defects in neuron morphology due to GRIP1 malfunction can be reversed. One way is to overexpress GRIP1. This leads to increased, but not complete recovery of branching. Another protein, EphB2, which interacts with GRIP1, can be mutated such that a 70-90% recovery of branching is possible. However, overexpression of the wild type leads to a decrease in neuron count.

Motor proteins such as Kinesin (KIF5) are bound to adapter molecules. Adapter molecules serves as a middle man to hold different molecules together. Adapter molecules like GRIP1 target specific loads which helps to move cargo from the Golgi to the extremities of a neuron cell. GRIP1 and KIF5 are very commonly found together due to a good binding affinity (Kd range from 10-20 nM ). As for how cargo gets to the right place, there has been a hypothesis called the “smart motor”. It is currently thought that the “smart motor” recognizes the difference between axonal (coated with KLC protein) and dendritic (coated with KHC) proteins. The destination is chosen accordingly. Unfortunately, details about the intermediate transporting steps are unknown. However, at the destination the binding of signaling protein 14-3-3 disrupts the interaction between KIF5 and GRIP1. This releases the cargo. In short, GRIP1 acts as a temporary glue between a microtubule motor like KIF5 and the cargo to be transported. If the bond between the adapter and the motor is unavailable, the cargo (e.g. EphB2) isn't able to be transported and remains in the golgi.