cell polarity is maintained in part by targeted vesicular trafficking to the apical and basolateral membrane domains as well as the primary cilium of polarized cells . the cilium is a rod - like organelle featured on the apical plasma membrane domain on most epithelial cells in vertebrates ,
increasing evidence indicates that polarized cell homeostasis is strongly affected by the  health of primary cilia , perhaps because cilia are needed for numerous cell signaling pathways such as polycystin , wnt , and hedgehog signaling .
acute deciliation can result in the loss of polarity in cells , implying an important role for the cilium in maintaining cell polarity .
furthermore , the loss of ciliary function is associated with cystic livers and kidneys as observed in bardet - biedl syndrome ( bbs ) and autosomal dominant polycystic kidney disease ( adpkd ) .
the exocyst is a highly conserved complex with important roles in mediating targeted vesicular trafficking in polarized cells .
the exocyst is an eight - subunit complex ( sec3 , sec5 , sec6 , sec8 , sec10 , sec15 , exo70 , and exo84 ) that was first identified as a requirement for exocytosis of vesicles at the bud tips of yeast .
in addition , the small gtpase sec4 is essential for post - golgi trafficking in yeast , and the exocyst complex functions as an effector for sec4 .
a current model of the exocyst delineates its function as a tethering complex in the trafficking of vesicles from a post - golgi compartment , the recycling endosome , to the basolateral plasma membrane in columnar epithelial cells . to accomplish this task , the exocyst associates with vesicles that contain the epithelial cell - specific clathrin adaptor complex ap-1b .
this process is regulated by the small gtpases rab8 , rab10 , cdc42 , and rala .
biochemical data indicate that both sec5 and exo84 interact with rala in its gtp - bound form [ 13 - 16 ] , and structural and biochemical work further reveals that sec5 and exo84 competitively bind to active rala , suggesting that rala plays an important role in regulating exocyst assembly .
these data established a role for the exocyst in basolateral sorting of cargo in polarized epithelial cells ( figure 1 , arrow 1 ) .
the sorting of biosynthetic cargos to different plasma membrane domains takes place either at the trans - golgi network ( tgn ) or in recycling endosomes in polarized epithelial cells .
vesicular trafficking to the cilium may originate in recycling endosomes where rab8 or rab11 or both may regulate the organization of distinct subdomains .
the exocyst has been shown to play a role in vesicular trafficking from the recycling endosomes ( re ) to the basolateral membrane ( arrow 1 ) as well as in trafficking to the cilium in association with rab8 , rabin8 , and rab11 ( arrow 2 ) .
vesicles may be directed to the base of the cilium by the interaction of rabin8 and bbs1 .
rab11 also has a known role in sorting to the apical membrane ( arrow 3 ) .
over the last couple of years , there has been mounting evidence that the exocyst also plays a role in vesicular trafficking to the cilium .
were the first to show localization of the exocyst subunits sec6/8 at the base of the primary cilium in addition to its known localization just below the tight junctions .
they also demonstrated that sec6/8 are overexpressed in adpkd primary cell cultures and immortalized cell lines , suggesting a link between the ciliopathy adpkd and the exocyst .
a recent study then demonstrated a direct role for the exocyst in primary ciliogenesis and cystogenesis in madin - darby canine kidney ( mdck ) cells .
knockdown of sec10 in mdck cells resulted in a decrease in cilium length which could be rescued with exogenous sec10 expression .
in addition , knockdown of sec10 resulted in decreased expression levels of sec8 and exo70 , indicating that sec10 may play a central role in exocyst organization at the cilium .
moreover , knockdown of sec10 decreased the levels of the intraflagellar transport protein 88 ( ift88 ) , suggesting that trafficking of ift88 to cilia may be exocyst - dependent . in the future , it will be interesting to learn whether similar findings will be observed with genetic mutations of sec10 or other exocyst components . notably , the exocyst is not the only component with a dual function in targeting to the basolateral membrane and cilia .
rab8a , which was described as a gtpase involved mainly in regulating cargo sorting to the basolateral membrane , was recently shown to localize to the primary cilium membrane in human retinal pigmented epithelial cells and to function in primary cilium formation .
similarly , in cilia - derived sensory organelles , the rod outer segments , rab8 plays a role in docking and fusion of rhodopsin transport carriers ( rtcs ) , and rab8 co - localizes with sec8 in the vicinity of rtc fusion sites in rana berlandieri frog cells .
interestingly , the rab8 guanine nucleotide exchange factor rabin8 interacts directly with the bbs1 subunit of a multimeric complex , the bbsome , that localizes at the base of the cilium and regulates ciliary membrane biogenesis .
biochemical data indicate that rabin8 may interact with sec15 and gtp - loaded rab11 ( wei guo , personal communication ) .
furthermore , rab11 has been shown to bind to the c - terminus of sec15 [ 26 - 28 ] , indicating a cooperative action between the exocyst and rab8 and rab11 gtpases in regulating vesicular trafficking to the primary cilium ( figure 1 , arrow 2 ) . the role of the exocyst in sorting to cilia or cilia - derived structures seems to be conserved from invertebrates to vertebrates , although the majority of epithelial cells in invertebrates do not contain cilia .
however , drosophila photoreceptor cells have a light - sensing microtubule structure on their apical stalk membrane .
sorting of rhodopsin1 to rhabdomeres and rhabdomere formation are also dependent on sec6 , sec15 , and rab11 function , highlighting the importance of the exocyst in cilia formation .
, this should soon change with the identification of players involved in this pathway . in the effort to establish a model ,
certain questions become apparent . for example , it is intriguing to note that the exocyst and rab8 are used for both cilium outgrowth and sorting to the basolateral membrane , whereas rab11 plays a role in cilium biogenesis in addition to its known function in regulating apical delivery of the polymeric iga receptor as it transcytoses from the basolateral to the apical membrane ( figure 1 , arrow 3 ) .
how are these different pathways delineated ? given the known localization of rab8 , rab11 , and the exocyst in different areas of recycling endosomes , it seems conceivable to assume that the pathway to the cilium involving these components may be originating in recycling endosomes .
perhaps the recycling endosomes are organized in three subdomains , each regulating a specific trafficking step and thereby preventing missorting of apical or basolateral cargos into the cilium .
indeed , the organization of recycling endosomes into apical and basolateral domains is so dramatic that they are often referred to as 
apical recycling endosomes and  central recycling endosomes ( for a detailed discussion of this topic , see ) . perhaps rab8 and rab11
another unknown is where vesicles that are targeted to the cilia fuse with the ciliary membrane .
perhaps they are directed first to the base of the cilium via the interaction between rabin8 and bbs1 . from the base of the cilium
, vesicles may be directed into the cilium on microtubule tracks because sec10 stains the entire length of the cilia membrane , implying that fusion of vesicles takes place along the ciliary membrane ; however , it is not clear whether such fusion might occur as there is currently no evidence for the presence of transport vesicles in cilia .
alternatively , fusion of vesicles may occur at the base of the cilium , thereby leading to the outgrowth of ciliary membrane . as researchers continue to make strides toward understanding the role of the exocyst in polarized epithelial cells , mechanisms of how one
 the role of the exocyst complex has been studied mainly in the context of basolateral sorting of cargos in polarized cells . 
 recent developments indicate an extended yet specific function of the exocyst in the outgrowth of the primary cilium from the apical membrane , thereby highlighting a role for the exocyst in ensuring membrane trafficking to important signaling stations in the cell , the tight junctions , and the cilia . 
Introduction and context
Major recent advances
Future directions
Competing interests