22 Philip Siekevitz 



mitochondria with the ER could faciUtate the removal of mito- 

 chondrial products, including carbon dioxide, to the outside 

 through this mechanism; in other words, the vesicular systems 

 of the cell are not static entities but behave as intrusion and 

 extrusion machines. It can be proposed that the regulation of 

 the input and the output of the cell, which was formerly 

 thought to be due only to the active metabolism of a spatially 

 fixed cell membrane, is now thought to be due also to an 

 extensive system of membranes which move within the cell 

 and which fuse with the cell membrane and are really adjuncts 

 of the cell membrane. Palade (1953) and Bennett (1956) have 

 pictured this concept, even with the idea that the membranes 

 are not passive in this regard but actively flow and perhaps 

 pump materials through the intracisternal spaces, either from 

 outside the cell inwards via the pinocytic vesicles, or from 

 inwards to the outside by means of that part of the agranular 

 reticulum which is connected with the granular reticulum of 

 the ER. Bennett (1956) also postulates that there are 

 specific binding sites on these membranes to account for the 

 selectivity of compounds moving in and out of the cell. Palay 

 (1958) has given a detailed description of the relationship 

 iDctween the extracellular space and the intracisternal spaces 

 of the ER and has postulated a similar theory of secretion 

 based on his morphological observations. 



Now what does all this mean, first in terms of permeability? 

 We can all immediately understand that the old concept of 

 intracellular space and extracellular space has to be refined 

 (cf. Palade, 1956a). Most of the experiments having to do 

 with permeability, by measuring the uptake or output of 

 compounds, be they charged ions or uncharged organic com- 

 pounds, will now have to be re-examined. For is not the 

 fluid inside the pinocytic vesicles still extracellular, the com- 

 pounds within still having to pass a membrane, either 

 passively, actively, or by membrane dissolution, before they 

 can mix with compounds in the cytoplasmic matrix? And 

 conversely, is it not possible that compounds within the 

 secretory granules — which are later shown to be formed from 



