Cruising along Microtubule Highways: How Membranes Move through the Secretory Pathway

ow microtubules (MTs) 1 influence secretion has long intrigued cell biologists. Significant insight has come from studies showing that MTs serve as highways along which transport intermediates travel between the ER and Golgi (9, 10, 21, 28, 32), making it tempting to conclude that MTs are essential for secretion. While the literature contains many additional reports supporting that view (for example 7, 31), it is also oddly replete with reports that secretion is unimpaired in cells depleted of MTs (for example 12, 18, 39, 41). Thus, although MTs are used for some steps in secretion, they may not always be required. To understand fully the role of MTs in secretion, it is therefore necessary to look beyond the question of whether secretion can occur when MTs are absent, but focus instead on how biosynthetic products are transported through the secretory pathway in the presence of MTs and how removal of MTs modifies normal transport mechanisms. We present here a multifaceted perspective that ties together a confusing body of evidence about MTs and secretion. By recalling the classic example of fast axonal transport, we emphasize that cell morphology dramatically influences the extent to which MTs are required for secretion. By summoning more contemporary cultured cell data, we note that transport between the ER and Golgi can occur efficiently in the absence of MTs, but only under restricted conditions. Finally, the variable MT requirement for transport between the ER and Golgi is explained in terms of how distinct compartments within the secretory pathway rely upon MTs for their spatial segregation and structural integrity and how removing MTs alters endomembrane organization in a manner whose effects on secretion are time dependent. Diffusion Cannot Account for Rapid Vesicle Transport