Fueled by microtubules: does tubulin dimer/polymer partitioning regulate intracellular metabolism?
Microtubules (MTs) or their subunits, tubulin dimers, interact with multiple components that contribute to intracellular metabolic pathways. MTs are required for insulin-dependent transport of glucose transporter 4 to the plasma membrane, they bind most glycolytic enzymes and are required for translation of the mRNA encoding hypoxia inducible factor-1α. Tubulin dimers bind the voltage-dependent anion channel of the mitochondrial outer membrane; this channel functions in metabolite transport in and out of mitochondria. We hypothesize that tubulin partitioning between dimer and polymer pools regulates multiple steps in metabolism, where metabolic output is greatest when both tubulin dimers and MT polymers are present and reduced by drug treatments that disrupt this normal balance. Experimental evidence from these drug-induced changes in tubulin dimer/polymer partitioning supports our model for several metabolic steps. Signal transduction pathways that stabilize or destabilize MTs can shift the normal ratio between unpolymerized and polymerized tubulin dimers, and one downstream consequence of this shift in tubulin partitioning could be a change in metabolic output.
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA. lc07@lehigh.edu
Lynne
L
Cassimeris
Victoria Caruso
VC
Silva
Elizabeth
E
Miller
Quynh
Q
Ton
Cody
C
Molnar
John
J
Fong
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
D011108:Polymers; D014404:Tubulin; D050994:Voltage-Dependent Anion Channels