TPV protein import into nucleus (matrix)

[gocentral]

GO:0006606 protein import into nucleus is a child of GO:0044743 intracellular protein transmembrane import but nucleocytoplasmic transport isn't "transmembrane" (the directed movement of proteins across a membrane) becasuse no membrane is traversed.

(this one might have come from the reasoner too?)

val

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/9880

[gocentral]

• summary: TPV protein improt into nucleus --> TPV protein import into nucleus (matrix)

Original comment by: ValWood

[gocentral]

• assigned_to: nobody --> ukemi

Original comment by: ukemi

[gocentral]

Traversing the nuclear membrane doesn't count? Agreed the nuclear pore is different from most transporters that move specific molecules, but in all the cases I know, a protein or RNA assembles with specific carrier proteins to form a complex that traverses the pore, crossing the nuclear envelope, in a specific direction. Specificity is determined by carrier-cargo interactions, and direction by location of the carriers and cargoes and by GTP binding and hydrolysis as transport complexes assemble and disassemble. Or have I completely missed the point here?

Original comment by: deustp01

[gocentral]

Hi Peter

Transmembrane transport is defined as" transported from one side of a membrane to the other" but in nucleocytoplasmic transport the lipid bilayer isn't traversed. http://tinyurl.com/c5f2nbp

This allows us to distinguish between nucleocytoplasmic and transmembrane transport in enrichments and slims as they are very different gene characteristics (in terms of viability/ expression, conservation etc)

Does that sound OK?

Val

Original comment by: ValWood

[gocentral]

Hi Val, The nuclear envelope has two lipid bilayer membranes and the pore mediates the transport of cargo macromolecules across both of them at one go. So saying that no lipid bilayer membrane is crossed still sounds wrong, but there are plenty of other differentia to put what a nuclear pore complex does in a separate function class from what a standard transmembrane transporter does. Are we getting closer? Peter

Original comment by: deustp01

[gocentral]

Hi Val,

I agree with Peter. Even in the figure you sent, the nuclear envelope is clear.

David

Original comment by: ukemi

[gocentral]

I still think that they are distinct transport systems Does this help: Summary: Transmembrane transport requires transport of a solute across a lipid bilayer. Note that transport through the nuclear pore complex is not transmembrane because the nuclear membrane is a double membrane and is not traversed. For transport through the nuclear pore, consider instead the term 'nucleocytoplasmic transport ; GO:0006913' and its children.

Its a topology distinction, a memebrane is NOT traversed in nucleocytoplasmic transsport (this would take you into the lumnen....)

see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030690/ As a result of this compartmentalization, sophisticated transport systems have evolved which mediate and regulate macromolecular transport between different subcellular locations.1 In transmembrane transport, membrane-embedded protein translocators directly transport proteins from the cytosol across an intracellular membrane. In vesicular transport, cargo is ferried between membrane-bound organelles via membrane-enclosed intermediates, such as spherical vesicles, which are stabilized by protein coats that are reminiscent of cages. A third major transport system refers to the selective macromolecular transport in and out of the nucleus, which is exclusively mediated by nuclear pore complexes (NPCs). NPCs are embedded into circular openings of the nuclear envelope (NE), thus resembling “biological grommets”.2,3 The NE is formed by two closely juxtaposed membranes, termed the inner nuclear membrane (INM) and outer nuclear membrane (ONM). The INM contains a unique set of membrane proteins that bind to chromatin and the nuclear lamina inside the nucleus.4,5 The INM proteins establish connections with the cytoskeleton via interactions with ONM proteins inside the lumen of the NE.6,7 While the proteins in the INM generally attach to densely-packed heterochromatin, NPCs are typically associated with actively transcribed, loosely-packed euchromatic regions.8 Thus, the NE, together with the embedded NPCs, is an important interface between the nucleus and the cytosol that is involved in nucleocytoplasmic transport, chromatin organization, replication-coupled DNA repair, regulation of gene expression, nuclear positioning, and nuclear migration among other cellular processes.

Val (Midori agrees)

Original comment by: ValWood

[gocentral]

The point Val is trying to make is that topologically, anything transported through a nuclear pore ends up on the same side of the lipid bilayer that forms the membranes of the nuclear envelope. To me, it's not about whether membranes are "crossed" or "traversed" or whatever; thats's a semantic angle that seems to be adding to the confusion. Instead, I get my head round it by concentrating on the topological relation between the origin and destination of the cargo.

Movement into or out of the nuclear envelope lumen, starting from either the nuclear lumen or the cytoplasm, is transmembrane, because the cargo starts on one side of a bilayer and ends up on the other.

For maximal accuracy, s/(Midori agrees)/(Midori understands Val's POV and is otherwise neutral)/.

Original comment by: mah11

[gocentral]

I think we agree that the processes by which macromolecules traverse the nuclear envelope via the nuclear pore are qualitatively different from the ones by which macro- and micromolecules traverse single lipid bilayer membranes and both can probably also be qualitatively distinguished from the processes by which molecules enter plastids. However, all of these structures do have lipid bilayer membranes bounding them and those lipid bilayers play a central role in creating the barrier that necessitates a transport process in the first place, so using presence / absence of a lipid bilayer as differentia to tell the processes apart seems odd.

Original comment by: deustp01

[gocentral]

Agreed as to Midori's topology. But this then is the same topology as for transport through a gap junction: cargo starts in the cytosol of a cell, enters the transport complex (junction here; nuclear pore before), traverses two successive bilayer membranes and a space between them, and emerges in the cytosol of another cell (in the np case, in the nuclear lumen, which is topologically equivalent to that second cell cytosol). So, still another distinct mode of transport to join conventional transporters and pumps, the nuclear pore complex, and transport of macromolecules into plastids. The differentia certainly include numbers of lipid bilayers traversed and traversal strategy. My only objection is that presence of some form of a lipid bilayer barrier per se is a common feature in all these cases.

Original comment by: deustp01

[gocentral]

Hi, I think the gap junction topology is different to the nuclear pore (2 membrane are physically traversed, but in the nuclear pore example no membrane is physically traversed because of the way that the inner and outer membrane are organised with respect to the pore complex. I would still call the gap junction "transmembrane".

However, I agree that the differentia we use currently are really, really confusing. I have asked a fission yeast expert in nucleocytoplasmic transport (Shelly Sazer, BCM) to help. She sees the problem and is going to converse with a colleague who works on membrane transport to see if they can suggest some clearer differentia.

In the meantime, can we remove the links between "protein import into nucleus" and "transmembrane transport"

Thanks

Val

Original comment by: ValWood

[gocentral]

Hi Val,

We discussed this yesterday on our ontology editors' call and decided that we agreed with you that from a topological perspective, a membrane is not physically crossed in this process. I have removed the transmembrane link.

David

Original comment by: ukemi

[gocentral]

• status: open --> closed-accepted

Original comment by: ukemi