I've written much about the Nuclear Pore Complex (NPC). This large molecular gate controls the flow of molecules into and out of the nucleus. Recent work (see this post and this new paper) describes how filaments containing "FG repeats" form a matrix in the center of the pore that blocks the movement of large but not small particles. To cross the pore (the black blobs in the pic below), big macromolecules must associate with factors (or nuclear transport receptors, NTRs - red blobs) that can melt and become part of the matrix (the squiggly spaghetti strings).
From a top-down view, the NPC looks like a large ring with 8-fold symmetry. It is composed of many proteins ... including some weird ones. For example one of the components of the NPC is sec13. Why is it called sec13? Well in a famous screen, R. Schekman's group isolated mutant yeast strains that were defective in transporting newly synthesized secreted proteins. Some mutants couldn't pump newly synthesized proteins into the endoplasmic reticulum (ER), other mutants had problems generating vesicles that are full of these newly made proteins and bud off of the ER, yet other strains were defective in how these vesicles fused with the Golgi, and still more mutants were identified that had problems transporting this protein cargo from the Golgi to the plasma membrane. Well Sec13 is a small protein that promotes the budding of vesicles off of the ER. So Sec13 had two lives. That of a protein that promotes ER to Golgi transport and that of a NPC protein. Now as strange as that might be, there is some weird connection between the ability to secrete proteins and proper NPC assembly. A couple of groups found that if you disrupt ER to Golgi transport you partially disassemble the NPC. Now it is true that the nuclear envelope is continuous with the ER but there may be some more fundamental connection between the two processes.
OK lets get back to the NPC weirdness ... in a new paper, the group that originally identified Sec13 as a constituent of the NPC, has now identified another oddball NPC component ... Dynein Light Chain.
Yes very weird.
Dynein is a giant molecular motor that can walk towards the minus ends of microtubles. It plays may roles in cells including flagellar movement, transport of vesicles, positioning of the nucleus, centering the MTOC, and attachment of microtubule ends to the kinetochores during mitosis. Now dynein is composed of many subunits, the most important being dynein heavy chain where all the motor activity is located. Dynein light chain does not utilize ATP (i.e. energy), or have motor activity, but instead helps the heavy chain do its job.
In this new paper, data is presented that suggests that dynein light chain has a second life, as a key structural component of the NPC. To back up this finding, the authors provide genetic data (in yeast), biochemical data, and some great electron-microscopy tomography as shown bellow:
If we think back to sec13 being part of the NPC, there seems to be some connection between the NPC and secretion. There is an idea out there that the cell may actively monitor whether it can secrete proteins, and if it can't it inhibits transport across the NPC. Some have dubbed this connection between the two processes, the Arrest of Secretion Response (ASR). So is there any connection between the NPC and microtubule based transport? In S. cerevisiae (budding yeast), microtubules are used mostly to move the nucleus and chromosomes around so it is unlikely that this link between the NPC and dynein is another example of ASR.
Any ideas?
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